ERBB2_HUMAN
ID ERBB2_HUMAN Reviewed; 1255 AA.
AC P04626; B2RZG3; B4DHN3; Q14256; Q6LDV1; Q9UMK4; X5D2V5;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 264.
DE RecName: Full=Receptor tyrosine-protein kinase erbB-2;
DE EC=2.7.10.1;
DE AltName: Full=Metastatic lymph node gene 19 protein;
DE Short=MLN 19;
DE AltName: Full=Proto-oncogene Neu;
DE AltName: Full=Proto-oncogene c-ErbB-2;
DE AltName: Full=Tyrosine kinase-type cell surface receptor HER2;
DE AltName: Full=p185erbB2;
DE AltName: CD_antigen=CD340;
DE Flags: Precursor;
GN Name=ERBB2; Synonyms=HER2, MLN19, NEU, NGL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3003577; DOI=10.1038/319230a0;
RA Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N.,
RA Saito T., Toyoshima K.;
RT "Similarity of protein encoded by the human c-erb-B-2 gene to epidermal
RT growth factor receptor.";
RL Nature 319:230-234(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT ALA-1170.
RX PubMed=2999974; DOI=10.1126/science.2999974;
RA Coussens L., Yang-Feng T.L., Liao Y.C., Chen E., Gray A., McGrath J.,
RA Seeburg P.H., Libermann T.A., Schlessinger J., Francke U., Levinson A.,
RA Ullrich A.;
RT "Tyrosine kinase receptor with extensive homology to EGF receptor shares
RT chromosomal location with neu oncogene.";
RL Science 230:1132-1139(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-452; VAL-655 AND
RP ALA-1170.
RG NIEHS SNPs program;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RA Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A.,
RA Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y.,
RA Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T.,
RA Sugano S., Nomura N., Isogai T.;
RT "NEDO human cDNA sequencing project focused on splicing variants.";
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-191 (ISOFORM 1).
RX PubMed=3039351; DOI=10.1128/mcb.7.7.2597-2601.1987;
RA Tal M., King C.R., Kraus M.H., Ullrich A., Schlessinger J., Givol D.;
RT "Human HER2 (neu) promoter: evidence for multiple mechanisms for
RT transcriptional initiation.";
RL Mol. Cell. Biol. 7:2597-2601(1987).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-867 (ISOFORM 6).
RC TISSUE=Fetal brain;
RX PubMed=24722188; DOI=10.1038/ncomms4650;
RA Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M.,
RA Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I.,
RA Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A.,
RA Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D.,
RA Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.;
RT "Protein interaction network of alternatively spliced isoforms from brain
RT links genetic risk factors for autism.";
RL Nat. Commun. 5:3650-3650(2014).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 737-1031.
RX PubMed=2995967; DOI=10.1073/pnas.82.19.6497;
RA Semba K., Kamata N., Toyoshima K., Yamamoto T.;
RT "A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-
RT 1/epidermal growth factor-receptor gene and is amplified in a human
RT salivary gland adenocarcinoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6497-6501(1985).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 832-909.
RC TISSUE=Mammary carcinoma;
RX PubMed=2992089; DOI=10.1126/science.2992089;
RA King C.R., Kraus M.H., Aaronson S.A.;
RT "Amplification of a novel v-erbB-related gene in a human mammary
RT carcinoma.";
RL Science 229:974-976(1985).
RN [11]
RP NUCLEOTIDE SEQUENCE OF 1081-1245, AND VARIANT ALA-1170.
RX PubMed=8104414; DOI=10.1089/dna.1993.12.611;
RA Sarkar F.H., Ball D.E., Li Y.W., Crissman J.D.;
RT "Molecular cloning and sequencing of an intron of Her-2/neu (ERBB2) gene.";
RL DNA Cell Biol. 12:611-615(1993).
RN [12]
RP INTERACTION WITH ERBB4, AND FUNCTION IN ACTIVATION OF STAT5A.
RX PubMed=10358079; DOI=10.1074/jbc.274.24.17209;
RA Olayioye M.A., Beuvink I., Horsch K., Daly J.M., Hynes N.E.;
RT "ErbB receptor-induced activation of stat transcription factors is mediated
RT by Src tyrosine kinases.";
RL J. Biol. Chem. 274:17209-17218(1999).
RN [13]
RP IDENTIFICATION IN A COMPLEX WITH PIK3C2A AND EGFR, IDENTIFICATION IN A
RP COMPLEX WITH PIK3C2B AND EGFR, AND INTERACTION WITH PIK3C2B.
RX PubMed=10805725; DOI=10.1128/mcb.20.11.3817-3830.2000;
RA Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D.,
RA Domin J.;
RT "Class II phosphoinositide 3-kinases are downstream targets of activated
RT polypeptide growth factor receptors.";
RL Mol. Cell. Biol. 20:3817-3830(2000).
RN [14]
RP INTERACTION WITH MUC1.
RX PubMed=12939402;
RA Li Y., Yu W.-H., Ren J., Chen W., Huang L., Kharbanda S., Loda M., Kufe D.;
RT "Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent
RT on the DF3/MUC1 oncoprotein.";
RL Mol. Cancer Res. 1:765-775(2003).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15380516; DOI=10.1016/j.ccr.2004.07.012;
RA Wang S.C., Lien H.C., Xia W., Chen I.F., Lo H.W., Wang Z., Ali-Seyed M.,
RA Lee D.F., Bartholomeusz G., Ou-Yang F., Giri D.K., Hung M.C.;
RT "Binding at and transactivation of the COX-2 promoter by nuclear tyrosine
RT kinase receptor ErbB-2.";
RL Cancer Cell 6:251-261(2004).
RN [16]
RP INTERACTION WITH PLXNB1.
RX PubMed=15210733; DOI=10.1083/jcb.200312094;
RA Swiercz J.M., Kuner R., Offermanns S.;
RT "Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine
RT kinase ErbB-2.";
RL J. Cell Biol. 165:869-880(2004).
RN [17]
RP INTERACTION WITH MEMO1.
RX PubMed=15156151; DOI=10.1038/ncb1134;
RA Marone R., Hess D., Dankort D., Muller W.J., Hynes N.E., Badache A.;
RT "Memo mediates ErbB2-driven cell motility.";
RL Nat. Cell Biol. 6:515-522(2004).
RN [18]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND INTERACTION WITH
RP KPNB1; RANBP2; CRM1; EEA1 AND CLTC.
RX PubMed=16314522; DOI=10.1128/mcb.25.24.11005-11018.2005;
RA Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G.,
RA Wang S.C., Hung M.C.;
RT "Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell
RT surface receptor.";
RL Mol. Cell. Biol. 25:11005-11018(2005).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1248, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [20]
RP FUNCTION, ALTERNATIVE INITIATION (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF MET-611; MET-687; MET-706 AND MET-712.
RX PubMed=16794579; DOI=10.1038/sj.emboj.7601191;
RA Anido J., Scaltriti M., Bech Serra J.J., Santiago Josefat B., Todo F.R.,
RA Baselga J., Arribas J.;
RT "Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative
RT initiation of translation.";
RL EMBO J. 25:3234-3244(2006).
RN [21]
RP INTERACTION WITH ERBB4, AND AUTOPHOSPHORYLATION IN TRANS.
RX PubMed=16978839; DOI=10.1016/j.cellsig.2006.07.020;
RA Li Z., Mei Y., Liu X., Zhou M.;
RT "Neuregulin-1 only induces trans-phosphorylation between ErbB receptor
RT heterodimer partners.";
RL Cell. Signal. 19:466-471(2007).
RN [22]
RP PHOSPHORYLATION AT TYR-1248.
RX PubMed=17554007; DOI=10.1523/jneurosci.5381-06.2007;
RA Deng S., Hirschberg A., Worzfeld T., Penachioni J.Y., Korostylev A.,
RA Swiercz J.M., Vodrazka P., Mauti O., Stoeckli E.T., Tamagnone L.,
RA Offermanns S., Kuner R.;
RT "Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and
RT patterning of the developing nervous system in vivo.";
RL J. Neurosci. 27:6333-6347(2007).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1054, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1054, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP INTERACTION WITH PTK6, AND ACTIVITY REGULATION.
RX PubMed=18719096; DOI=10.1073/pnas.0805009105;
RA Xiang B., Chatti K., Qiu H., Lakshmi B., Krasnitz A., Hicks J., Yu M.,
RA Miller W.T., Muthuswamy S.K.;
RT "Brk is coamplified with ErbB2 to promote proliferation in breast cancer.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12463-12468(2008).
RN [26]
RP FUNCTION IN NUCLEUS.
RX PubMed=19372587; DOI=10.1158/1541-7786.mcr-08-0316;
RA Hawthorne V.S., Huang W.C., Neal C.L., Tseng L.M., Hung M.C., Yu D.;
RT "ErbB2-mediated Src and signal transducer and activator of transcription 3
RT activation leads to transcriptional up-regulation of p21Cip1 and
RT chemoresistance in breast cancer cells.";
RL Mol. Cancer Res. 7:592-600(2009).
RN [27]
RP INTERACTION WITH CPNE3.
RX PubMed=20010870; DOI=10.1038/onc.2009.456;
RA Heinrich C., Keller C., Boulay A., Vecchi M., Bianchi M., Sack R.,
RA Lienhard S., Duss S., Hofsteenge J., Hynes N.E.;
RT "Copine-III interacts with ErbB2 and promotes tumor cell migration.";
RL Oncogene 29:1598-1610(2010).
RN [28]
RP FUNCTION.
RX PubMed=20937854; DOI=10.1073/pnas.1000975107;
RA Zaoui K., Benseddik K., Daou P., Salaun D., Badache A.;
RT "ErbB2 receptor controls microtubule capture by recruiting ACF7 to the
RT plasma membrane of migrating cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18517-18522(2010).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1107, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [30]
RP CHROMOSOMAL REARRANGEMENT WITH CDK12.
RX PubMed=21097718; DOI=10.1158/0008-5472.can-10-1749;
RA Zang Z.J., Ong C.K., Cutcutache I., Yu W., Zhang S.L., Huang D., Ler L.D.,
RA Dykema K., Gan A., Tao J., Lim S., Liu Y., Futreal P.A., Grabsch H.,
RA Furge K.A., Goh L.K., Rozen S., Teh B.T., Tan P.;
RT "Genetic and structural variation in the gastric cancer kinome revealed
RT through targeted deep sequencing.";
RL Cancer Res. 71:29-39(2011).
RN [31]
RP FUNCTION IN NUCLEUS, INTERACTION WITH ACTB AND RPA194, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21555369; DOI=10.1158/0008-5472.can-10-3504;
RA Li L.Y., Chen H., Hsieh Y.H., Wang Y.N., Chu H.J., Chen Y.H., Chen H.Y.,
RA Chien P.J., Ma H.T., Tsai H.C., Lai C.C., Sher Y.P., Lien H.C., Tsai C.H.,
RA Hung M.C.;
RT "Nuclear ErbB2 enhances translation and cell growth by activating
RT transcription of ribosomal RNA genes.";
RL Cancer Res. 71:4269-4279(2011).
RN [32]
RP INTERACTION WITH EGFR.
RX PubMed=21190959; DOI=10.1210/en.2010-0940;
RA Kharmate G., Rajput P.S., Watt H.L., Somvanshi R.K., Chaudhari N., Qiu X.,
RA Kumar U.;
RT "Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in
RT the presence of somatostatin receptor 5 modulate signaling pathways.";
RL Endocrinology 152:931-945(2011).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1054, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-182; SER-1054; SER-1083 AND
RP THR-1166, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1054 AND SER-1151, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [36]
RP INTERACTION WITH HSP90AA1 AND HSP90AB1.
RX PubMed=26517842; DOI=10.1371/journal.pone.0141786;
RA Prince T.L., Kijima T., Tatokoro M., Lee S., Tsutsumi S., Yim K., Rivas C.,
RA Alarcon S., Schwartz H., Khamit-Kush K., Scroggins B.T., Beebe K.,
RA Trepel J.B., Neckers L.;
RT "Client proteins and small molecule inhibitors display distinct binding
RT preferences for constitutive and stress-induced HSP90 isoforms and their
RT conformationally restricted mutants.";
RL PLoS ONE 10:E0141786-E0141786(2015).
RN [37]
RP PHOSPHORYLATION AT TYR-1112; TYR-1139; TYR-1196 AND TYR-1248, AND
RP DEPHOSPHORYLATION BY PTPN12.
RX PubMed=27134172; DOI=10.1016/j.celrep.2016.04.016;
RA Li H., Yang F., Liu C., Xiao P., Xu Y., Liang Z., Liu C., Wang H., Wang W.,
RA Zheng W., Zhang W., Ma X., He D., Song X., Cui F., Xu Z., Yi F., Sun J.P.,
RA Yu X.;
RT "Crystal structure and substrate specificity of PTPN12.";
RL Cell Rep. 15:1345-1358(2016).
RN [38]
RP INTERACTION WITH SORL1, AND SUBCELLULAR LOCATION.
RX PubMed=31138794; DOI=10.1038/s41467-019-10275-0;
RA Pietilae M., Sahgal P., Peuhu E., Jaentti N.Z., Paatero I., Naervae E.,
RA Al-Akhrass H., Lilja J., Georgiadou M., Andersen O.M., Padzik A., Sihto H.,
RA Joensuu H., Blomqvist M., Saarinen I., Bostroem P.J., Taimen P., Ivaska J.;
RT "SORLA regulates endosomal trafficking and oncogenic fitness of HER2.";
RL Nat. Commun. 10:2340-2340(2019).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 654-662 IN COMPLEX WITH HLA AND
RP BETA-2 MICROGLOBULIN.
RX PubMed=10593938; DOI=10.1074/jbc.274.51.36422;
RA Kuhns J.J., Batalia M.A., Yan S., Collins E.J.;
RT "Poor binding of a HER-2/neu epitope (GP2) to HLA-A2.1 is due to a lack of
RT interactions with the center of the peptide.";
RL J. Biol. Chem. 274:36422-36427(1999).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 1247-1255 IN COMPLEX WITH ERBIN,
RP AND INTERACTION WITH ERBIN.
RX PubMed=12444095; DOI=10.1074/jbc.c200571200;
RA Birrane G., Chung J., Ladias J.A.;
RT "Novel mode of ligand recognition by the Erbin PDZ domain.";
RL J. Biol. Chem. 278:1399-1402(2003).
RN [41]
RP STRUCTURE BY NMR OF 1135-1144 IN COMPLEX WITH GRB7, AND INTERACTION WITH
RP GRB7.
RX PubMed=12975581; DOI=10.1023/a:1025498409113;
RA Ivancic M., Daly R.J., Lyons B.A.;
RT "Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and
RT structural basis for Grb7 binding to ErbB2.";
RL J. Biomol. NMR 27:205-219(2003).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 23-629 IN COMPLEX WITH THE
RP ANTIBODY HERCEPTIN.
RX PubMed=12610629; DOI=10.1038/nature01392;
RA Cho H.-S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B.,
RA Denney D.W. Jr., Leahy D.J.;
RT "Structure of the extracellular region of HER2 alone and in complex with
RT the Herceptin Fab.";
RL Nature 421:756-760(2003).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 23-646 IN COMPLEX WITH THE
RP ANTIBODY PERTUZUMAB, INTERACTION WITH ERBB3, MUTAGENESIS OF
RP 317-LEU-HIS-318, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-187; ASN-259 AND
RP ASN-530.
RX PubMed=15093539; DOI=10.1016/s1535-6108(04)00083-2;
RA Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J., de Vos A.M.,
RA Sliwkowski M.X.;
RT "Insights into ErbB signaling from the structure of the ErbB2-pertuzumab
RT complex.";
RL Cancer Cell 5:317-328(2004).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 23-646 IN COMPLEX WITH THE
RP ANTIBODY HERCEPTIN, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-259 AND
RP ASN-530.
RX PubMed=19299620; DOI=10.1126/science.1165480;
RA Bostrom J., Yu S.F., Kan D., Appleton B.A., Lee C.V., Billeci K., Man W.,
RA Peale F., Ross S., Wiesmann C., Fuh G.;
RT "Variants of the antibody herceptin that interact with HER2 and VEGF at the
RT antigen binding site.";
RL Science 323:1610-1614(2009).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 23-646 IN COMPLEX WITH ENGINEERED
RP ANTIBODY ZHER2, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-68; ASN-259 AND
RP ASN-571.
RX PubMed=20696930; DOI=10.1073/pnas.1005025107;
RA Eigenbrot C., Ultsch M., Dubnovitsky A., Abrahmsen L., Hard T.;
RT "Structural basis for high-affinity HER2 receptor binding by an engineered
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:15039-15044(2010).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 703-1029 IN COMPLEX WITH
RP INHIBITOR SYR127063, CATALYTIC ACTIVITY, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=21454582; DOI=10.1074/jbc.m110.206193;
RA Aertgeerts K., Skene R., Yano J., Sang B.C., Zou H., Snell G., Jennings A.,
RA Iwamoto K., Habuka N., Hirokawa A., Ishikawa T., Tanaka T., Miki H.,
RA Ohta Y., Sogabe S.;
RT "Structural analysis of the mechanism of inhibition and allosteric
RT activation of the kinase domain of HER2 protein.";
RL J. Biol. Chem. 286:18756-18765(2011).
RN [47]
RP VARIANTS VAL-654 AND VAL-655.
RX PubMed=8095488; DOI=10.1006/geno.1993.1081;
RA Ehsani A., Low J., Wallace R.B., Wu A.M.;
RT "Characterization of a new allele of the human ERBB2 gene by allele-
RT specific competition hybridization.";
RL Genomics 15:426-429(1993).
RN [48]
RP INVOLVEMENT IN CANCER, VARIANT GASC SER-776, VARIANT OC SER-857, VARIANT
RP GLM LYS-914, AND VARIANTS LNCR PRO-755; ALA-TYR-VAL-MET-774 INS AND
RP VAL-GLY-SER-779 INS.
RX PubMed=15457249; DOI=10.1038/431525b;
RG Cancer genome project and collaborative group;
RA Stephens P., Hunter C., Bignell G., Edkins S., Davies H., Teague J.,
RA Stevens C., O'Meara S., Smith R., Parker A., Barthorpe A., Blow M.,
RA Brackenbury L., Butler A., Clarke O., Cole J., Dicks E., Dike A., Drozd A.,
RA Edwards K., Forbes S., Foster R., Gray K., Greenman C., Halliday K.,
RA Hills K., Kosmidou V., Lugg R., Menzies A., Perry J., Petty R., Raine K.,
RA Ratford L., Shepherd R., Small A., Stephens Y., Tofts C., Varian J.,
RA West S., Widaa S., Yates A., Brasseur F., Cooper C.S., Flanagan A.M.,
RA Knowles M., Leung S.Y., Louis D.N., Looijenga L.H., Malkowicz B.,
RA Pierotti M.A., Teh B., Chenevix-Trench G., Weber B.L., Yuen S.T.,
RA Harris G., Goldstraw P., Nicholson A.G., Futreal P.A., Wooster R.,
RA Stratton M.R.;
RT "Lung cancer: intragenic ERBB2 kinase mutations in tumours.";
RL Nature 431:525-526(2004).
RN [49]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-654; VAL-655; SER-768; ALA-1170 AND
RP ASP-1216, VARIANT GASC SER-776, AND VARIANT OC SER-857.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [50]
RP INVOLVEMENT IN VSCN2, VARIANT VSCN2 VAL-710, CHARACTERIZATION OF VARIANT
RP VSCN2 VAL-710, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=33497358; DOI=10.1172/jci145837;
RA Le T.L., Galmiche L., Levy J., Suwannarat P., Hellebrekers D.M.,
RA Morarach K., Boismoreau F., Theunissen T.E., Lefebvre M., Pelet A.,
RA Martinovic J., Gelot A., Guimiot F., Calleroz A., Gitiaux C., Hully M.,
RA Goulet O., Chardot C., Drunat S., Capri Y., Bole-Feysot C., Nitschke P.,
RA Whalen S., Mouthon L., Babcock H.E., Hofstra R., de Coo I.F., Tabet A.C.,
RA Molina T.J., Keren B., Brooks A., Smeets H.J., Marklund U., Gordon C.T.,
RA Lyonnet S., Amiel J., Bondurand N.;
RT "Dysregulation of the NRG1/ERBB pathway causes a developmental disorder
RT with gastrointestinal dysmotility in humans.";
RL J. Clin. Invest. 131:0-0(2021).
CC -!- FUNCTION: Protein tyrosine kinase that is part of several cell surface
CC receptor complexes, but that apparently needs a coreceptor for ligand
CC binding. Essential component of a neuregulin-receptor complex, although
CC neuregulins do not interact with it alone. GP30 is a potential ligand
CC for this receptor. Regulates outgrowth and stabilization of peripheral
CC microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1
CC signaling pathway elicits the phosphorylation and thus the inhibition
CC of GSK3B at cell membrane. This prevents the phosphorylation of APC and
CC CLASP2, allowing its association with the cell membrane. In turn,
CC membrane-bound APC allows the localization of MACF1 to the cell
CC membrane, which is required for microtubule capture and stabilization.
CC {ECO:0000305}.
CC -!- FUNCTION: In the nucleus is involved in transcriptional regulation.
CC Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter
CC and activates its transcription. Implicated in transcriptional
CC activation of CDKN1A; the function involves STAT3 and SRC. Involved in
CC the transcription of rRNA genes by RNA Pol I and enhances protein
CC synthesis and cell growth. {ECO:0000269|PubMed:10358079,
CC ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:21454582};
CC -!- ACTIVITY REGULATION: Activated by dimerization. Not activated by EGF,
CC TGF-alpha and amphiregulin. Interaction with PTK6 increases its
CC intrinsic kinase activity. {ECO:0000269|PubMed:18719096,
CC ECO:0000269|PubMed:21454582}.
CC -!- SUBUNIT: Homodimer (PubMed:21454582). Heterodimer with EGFR, ERBB3 and
CC ERBB4 (PubMed:10358079, PubMed:15093539, PubMed:21190959,
CC PubMed:16978839). Part of a complex with EGFR and either PIK3C2A or
CC PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1196
CC (PubMed:10805725). Interacts with PLXNB1 (PubMed:15210733). Interacts
CC (when phosphorylated on Tyr-1248) with MEMO1 (PubMed:15156151).
CC Interacts with MUC1; the interaction is enhanced by heregulin (HRG)
CC (PubMed:12939402). Interacts (when phosphorylated on Tyr-1139) with
CC GRB7 (via SH2 domain) (PubMed:12975581). Interacts (when phosphorylated
CC on Tyr-1248) with ERBIN (PubMed:12444095). Interacts with KPNB1,
CC RANBP2, EEA1, CRM1 and CLTC (PubMed:16314522). Interacts with PTK6
CC (PubMed:18719096). Interacts with RPA194 and ACTB (PubMed:21555369).
CC Interacts with PRKCABP, SRC and MYOC (By similarity). Interacts
CC (preferentially with the tyrosine phosphorylated form) with CPNE3; this
CC interaction occurs at the cell membrane and is increased in a growth
CC factor heregulin-dependent manner (PubMed:20010870). Interacts with
CC HSP90AA1 and HSP90AB1 in an ATP-dependent manner; the interaction
CC suppresses ERBB2 kinase activity (PubMed:26517842). Interacts with
CC SORL1; this interaction regulates ERBB2 subcellular distribution by
CC promoting its recycling after internalization from endosomes back to
CC the plasma membrane, hence stimulates ERBB2-mediated signaling
CC (PubMed:31138794). {ECO:0000250|UniProtKB:P70424,
CC ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10805725,
CC ECO:0000269|PubMed:12939402, ECO:0000269|PubMed:12975581,
CC ECO:0000269|PubMed:15093539, ECO:0000269|PubMed:15156151,
CC ECO:0000269|PubMed:15210733, ECO:0000269|PubMed:16314522,
CC ECO:0000269|PubMed:16978839, ECO:0000269|PubMed:18719096,
CC ECO:0000269|PubMed:20010870, ECO:0000269|PubMed:21190959,
CC ECO:0000269|PubMed:21454582, ECO:0000269|PubMed:21555369,
CC ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:31138794}.
CC -!- INTERACTION:
CC P04626; P00519: ABL1; NbExp=2; IntAct=EBI-641062, EBI-375543;
CC P04626; P42684: ABL2; NbExp=6; IntAct=EBI-641062, EBI-1102694;
CC P04626; P15309: ACP3; NbExp=2; IntAct=EBI-641062, EBI-1222012;
CC P04626; P60709: ACTB; NbExp=10; IntAct=EBI-641062, EBI-353944;
CC P04626; Q92625: ANKS1A; NbExp=2; IntAct=EBI-641062, EBI-1048612;
CC P04626; O00213: APBB1; NbExp=2; IntAct=EBI-641062, EBI-81694;
CC P04626; O75815: BCAR3; NbExp=2; IntAct=EBI-641062, EBI-702336;
CC P04626; Q9HB71: CACYBP; NbExp=2; IntAct=EBI-641062, EBI-1047302;
CC P04626; Q16543: CDC37; NbExp=3; IntAct=EBI-641062, EBI-295634;
CC P04626; Q9NSE2: CISH; NbExp=4; IntAct=EBI-641062, EBI-617866;
CC P04626; Q7Z7G1: CLNK; NbExp=2; IntAct=EBI-641062, EBI-7878194;
CC P04626; P46109: CRKL; NbExp=2; IntAct=EBI-641062, EBI-910;
CC P04626; Q93034: CUL5; NbExp=2; IntAct=EBI-641062, EBI-1057139;
CC P04626; Q99704: DOK1; NbExp=2; IntAct=EBI-641062, EBI-1384360;
CC P04626; Q8TEW6: DOK4; NbExp=2; IntAct=EBI-641062, EBI-6918542;
CC P04626; Q15075: EEA1; NbExp=5; IntAct=EBI-641062, EBI-298113;
CC P04626; P98172: EFNB1; NbExp=11; IntAct=EBI-641062, EBI-538287;
CC P04626; P00533: EGFR; NbExp=25; IntAct=EBI-641062, EBI-297353;
CC P04626; P04626: ERBB2; NbExp=12; IntAct=EBI-641062, EBI-641062;
CC P04626; P21860: ERBB3; NbExp=29; IntAct=EBI-641062, EBI-720706;
CC P04626; Q15303: ERBB4; NbExp=4; IntAct=EBI-641062, EBI-80371;
CC P04626; Q9UJM3: ERRFI1; NbExp=3; IntAct=EBI-641062, EBI-2941912;
CC P04626; P09769: FGR; NbExp=3; IntAct=EBI-641062, EBI-1383732;
CC P04626; P06241: FYN; NbExp=2; IntAct=EBI-641062, EBI-515315;
CC P04626; O75791: GRAP2; NbExp=2; IntAct=EBI-641062, EBI-740418;
CC P04626; P62993: GRB2; NbExp=5; IntAct=EBI-641062, EBI-401755;
CC P04626; Q14451: GRB7; NbExp=5; IntAct=EBI-641062, EBI-970191;
CC P04626; P07900: HSP90AA1; NbExp=5; IntAct=EBI-641062, EBI-296047;
CC P04626; P08238: HSP90AB1; NbExp=4; IntAct=EBI-641062, EBI-352572;
CC P04626; P14625: HSP90B1; NbExp=2; IntAct=EBI-641062, EBI-359129;
CC P04626; P46940: IQGAP1; NbExp=5; IntAct=EBI-641062, EBI-297509;
CC P04626; P35568: IRS1; NbExp=2; IntAct=EBI-641062, EBI-517592;
CC P04626; Q08881: ITK; NbExp=2; IntAct=EBI-641062, EBI-968552;
CC P04626; P23458: JAK1; NbExp=2; IntAct=EBI-641062, EBI-1383438;
CC P04626; Q14974: KPNB1; NbExp=14; IntAct=EBI-641062, EBI-286758;
CC P04626; Q96JA1: LRIG1; NbExp=7; IntAct=EBI-641062, EBI-2865191;
CC P04626; O75367: MACROH2A1; NbExp=6; IntAct=EBI-641062, EBI-2868511;
CC P04626; O75367-3: MACROH2A1; NbExp=3; IntAct=EBI-641062, EBI-6250866;
CC P04626; Q9UQF2: MAPK8IP1; NbExp=4; IntAct=EBI-641062, EBI-78404;
CC P04626; Q13387: MAPK8IP2; NbExp=3; IntAct=EBI-641062, EBI-722813;
CC P04626; P42679: MATK; NbExp=2; IntAct=EBI-641062, EBI-751664;
CC P04626; Q9Y316: MEMO1; NbExp=6; IntAct=EBI-641062, EBI-1104564;
CC P04626; O43639: NCK2; NbExp=2; IntAct=EBI-641062, EBI-713635;
CC P04626; Q02297-7: NRG1; NbExp=2; IntAct=EBI-641062, EBI-2460927;
CC P04626; O00750: PIK3C2B; NbExp=2; IntAct=EBI-641062, EBI-641107;
CC P04626; P27986: PIK3R1; NbExp=11; IntAct=EBI-641062, EBI-79464;
CC P04626; O00459: PIK3R2; NbExp=6; IntAct=EBI-641062, EBI-346930;
CC P04626; Q92569: PIK3R3; NbExp=9; IntAct=EBI-641062, EBI-79893;
CC P04626; P19174: PLCG1; NbExp=5; IntAct=EBI-641062, EBI-79387;
CC P04626; P16885: PLCG2; NbExp=3; IntAct=EBI-641062, EBI-617403;
CC P04626; O95602: POLR1A; NbExp=16; IntAct=EBI-641062, EBI-359472;
CC P04626; Q13882: PTK6; NbExp=4; IntAct=EBI-641062, EBI-1383632;
CC P04626; Q06124: PTPN11; NbExp=3; IntAct=EBI-641062, EBI-297779;
CC P04626; Q05209: PTPN12; NbExp=4; IntAct=EBI-641062, EBI-2266035;
CC P04626; Q99952: PTPN18; NbExp=6; IntAct=EBI-641062, EBI-1384210;
CC P04626; Q99952-1: PTPN18; NbExp=5; IntAct=EBI-641062, EBI-12739708;
CC P04626; P23467: PTPRB; NbExp=2; IntAct=EBI-641062, EBI-1265766;
CC P04626; P08575: PTPRC; NbExp=2; IntAct=EBI-641062, EBI-1341;
CC P04626; Q12913: PTPRJ; NbExp=2; IntAct=EBI-641062, EBI-2264500;
CC P04626; Q15262: PTPRK; NbExp=2; IntAct=EBI-641062, EBI-474052;
CC P04626; Q16827: PTPRO; NbExp=2; IntAct=EBI-641062, EBI-723739;
CC P04626; Q15256: PTPRR; NbExp=2; IntAct=EBI-641062, EBI-2265659;
CC P04626; P49792: RANBP2; NbExp=3; IntAct=EBI-641062, EBI-973138;
CC P04626; P20936: RASA1; NbExp=8; IntAct=EBI-641062, EBI-1026476;
CC P04626; O95980: RECK; NbExp=4; IntAct=EBI-641062, EBI-2823742;
CC P04626; Q9NP31: SH2D2A; NbExp=2; IntAct=EBI-641062, EBI-490630;
CC P04626; P29353: SHC1; NbExp=10; IntAct=EBI-641062, EBI-78835;
CC P04626; P98077: SHC2; NbExp=3; IntAct=EBI-641062, EBI-7256023;
CC P04626; Q92529: SHC3; NbExp=2; IntAct=EBI-641062, EBI-79084;
CC P04626; Q9H6Q3: SLA2; NbExp=2; IntAct=EBI-641062, EBI-1222854;
CC P04626; O15524: SOCS1; NbExp=2; IntAct=EBI-641062, EBI-968198;
CC P04626; P12931: SRC; NbExp=11; IntAct=EBI-641062, EBI-621482;
CC P04626; P42224: STAT1; NbExp=3; IntAct=EBI-641062, EBI-1057697;
CC P04626; P40763: STAT3; NbExp=9; IntAct=EBI-641062, EBI-518675;
CC P04626; P31948: STIP1; NbExp=2; IntAct=EBI-641062, EBI-1054052;
CC P04626; Q7KZ85: SUPT6H; NbExp=2; IntAct=EBI-641062, EBI-2515547;
CC P04626; P43405: SYK; NbExp=7; IntAct=EBI-641062, EBI-78302;
CC P04626; Q9Y490: TLN1; NbExp=3; IntAct=EBI-641062, EBI-2462036;
CC P04626; Q63HR2: TNS2; NbExp=4; IntAct=EBI-641062, EBI-949753;
CC P04626; Q68CZ2: TNS3; NbExp=2; IntAct=EBI-641062, EBI-1220488;
CC P04626; Q96D37: VAV1; NbExp=2; IntAct=EBI-641062, EBI-7875353;
CC P04626; P52735: VAV2; NbExp=3; IntAct=EBI-641062, EBI-297549;
CC P04626; O14980: XPO1; NbExp=2; IntAct=EBI-641062, EBI-355867;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:31138794, ECO:0000269|PubMed:33497358}; Single-pass
CC type I membrane protein. Early endosome {ECO:0000269|PubMed:31138794}.
CC Cytoplasm, perinuclear region. Nucleus. Note=Translocation to the
CC nucleus requires endocytosis, probably endosomal sorting and is
CC mediated by importin beta-1/KPNB1. Also detected in VPS35-positive
CC endosome-to-TGN retrograde vesicles (PubMed:31138794).
CC {ECO:0000269|PubMed:31138794}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=6;
CC Name=1; Synonyms=ERBB2, HER2;
CC IsoId=P04626-1; Sequence=Displayed;
CC Name=2; Synonyms=CTF-611;
CC IsoId=P04626-2; Sequence=VSP_039249;
CC Name=3; Synonyms=CTF-687;
CC IsoId=P04626-3; Sequence=VSP_039250;
CC Name=4;
CC IsoId=P04626-4; Sequence=VSP_039248;
CC Name=5;
CC IsoId=P04626-5; Sequence=VSP_054787;
CC Name=6; Synonyms=B;
CC IsoId=P04626-6; Sequence=VSP_055902, VSP_055903, VSP_055904;
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tumor tissues including
CC primary breast tumors and tumors from small bowel, esophagus, kidney
CC and mouth. {ECO:0000269|PubMed:15380516}.
CC -!- PTM: Autophosphorylated. Autophosphorylation occurs in trans, i.e. one
CC subunit of the dimeric receptor phosphorylates tyrosine residues on the
CC other subunit (Probable). Ligand-binding increases phosphorylation on
CC tyrosine residues (PubMed:27134172, PubMed:33497358). Signaling via
CC SEMA4C promotes phosphorylation at Tyr-1248 (PubMed:17554007).
CC Dephosphorylated by PTPN12 (PubMed:27134172).
CC {ECO:0000269|PubMed:17554007, ECO:0000269|PubMed:27134172,
CC ECO:0000269|PubMed:33497358, ECO:0000305}.
CC -!- POLYMORPHISM: There are four alleles due to the variations in positions
CC 654 and 655. Allele B1 (Ile-654/Ile-655) has a frequency of 0.782;
CC allele B2 (Ile-654/Val-655) has a frequency of 0.206; allele B3 (Val-
CC 654/Val-655) has a frequency of 0.012.
CC -!- DISEASE: Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant
CC central nervous system neoplasms derived from glial cells. They
CC comprise astrocytomas and glioblastoma multiforme that are derived from
CC astrocytes, oligodendrogliomas derived from oligodendrocytes and
CC ependymomas derived from ependymocytes. {ECO:0000269|PubMed:15457249}.
CC Note=The gene represented in this entry is involved in disease
CC pathogenesis.
CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer
CC defines malignancies originating from ovarian tissue. Although many
CC histologic types of ovarian tumors have been described, epithelial
CC ovarian carcinoma is the most common form. Ovarian cancers are often
CC asymptomatic and the recognized signs and symptoms, even of late-stage
CC disease, are vague. Consequently, most patients are diagnosed with
CC advanced disease. {ECO:0000269|PubMed:15457249,
CC ECO:0000269|PubMed:17344846}. Note=The gene represented in this entry
CC is involved in disease pathogenesis.
CC -!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting
CC tissues of the lung. The most common form of lung cancer is non-small
CC cell lung cancer (NSCLC) that can be divided into 3 major histologic
CC subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung
CC cancer. NSCLC is often diagnosed at an advanced stage and has a poor
CC prognosis. {ECO:0000269|PubMed:15457249}. Note=The gene represented in
CC this entry is involved in disease pathogenesis.
CC -!- DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which
CC starts in the stomach, can spread to the esophagus or the small
CC intestine, and can extend through the stomach wall to nearby lymph
CC nodes and organs. It also can metastasize to other parts of the body.
CC The term gastric cancer or gastric carcinoma refers to adenocarcinoma
CC of the stomach that accounts for most of all gastric malignant tumors.
CC Two main histologic types are recognized, diffuse type and intestinal
CC type carcinomas. Diffuse tumors are poorly differentiated infiltrating
CC lesions, resulting in thickening of the stomach. In contrast,
CC intestinal tumors are usually exophytic, often ulcerating, and
CC associated with intestinal metaplasia of the stomach, most often
CC observed in sporadic disease. {ECO:0000269|PubMed:15457249,
CC ECO:0000269|PubMed:17344846}. Note=The protein represented in this
CC entry is involved in disease pathogenesis.
CC -!- DISEASE: Note=Chromosomal aberrations involving ERBB2 may be a cause
CC gastric cancer. Deletions within 17q12 region producing fusion
CC transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to
CC truncated CDK12 protein not in-frame with ERBB2.
CC {ECO:0000269|PubMed:21097718}.
CC -!- DISEASE: Visceral neuropathy, familial, 2, autosomal recessive (VSCN2)
CC [MIM:619465]: An autosomal recessive disorder characterized by
CC intestinal dysmotility due to aganglionosis (Hirschsprung disease),
CC hypoganglionosis, and/or chronic intestinal pseudoobstruction. Patients
CC also show peripheral axonal neuropathy, hypotonia, mild developmental
CC delay, unilateral ptosis, and sensorineural hearing loss.
CC {ECO:0000269|PubMed:33497358}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at Met-
CC 611 of isoform 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation at Met-
CC 687 of isoform 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ERBB2ID162ch17q11.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/erbb2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=ERBB2 entry;
CC URL="https://en.wikipedia.org/wiki/ERBB2";
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DR EMBL; AH001455; AAA35808.1; -; Genomic_DNA.
DR EMBL; X03363; CAA27060.1; -; mRNA.
DR EMBL; M11730; AAA75493.1; -; mRNA.
DR EMBL; M12036; AAA35978.1; -; Genomic_DNA.
DR EMBL; AY208911; AAO18082.1; -; Genomic_DNA.
DR EMBL; AK295195; BAG58195.1; -; mRNA.
DR EMBL; CH471152; EAW60597.1; -; Genomic_DNA.
DR EMBL; BC167147; AAI67147.1; -; mRNA.
DR EMBL; M16792; AAA58637.1; -; Genomic_DNA.
DR EMBL; M16789; AAA58637.1; JOINED; Genomic_DNA.
DR EMBL; M16790; AAA58637.1; JOINED; Genomic_DNA.
DR EMBL; M16791; AAA58637.1; JOINED; Genomic_DNA.
DR EMBL; KJ534964; AHW56604.1; -; mRNA.
DR EMBL; L29395; AAA35809.1; -; Genomic_DNA.
DR EMBL; M95667; AAC37531.1; -; Genomic_DNA.
DR CCDS; CCDS32642.1; -. [P04626-1]
DR CCDS; CCDS45667.1; -. [P04626-5]
DR CCDS; CCDS74052.1; -. [P04626-4]
DR PIR; A24571; A24571.
DR RefSeq; NP_001005862.1; NM_001005862.2. [P04626-5]
DR RefSeq; NP_001276865.1; NM_001289936.1. [P04626-4]
DR RefSeq; NP_001276867.1; NM_001289938.1.
DR RefSeq; NP_004439.2; NM_004448.3. [P04626-1]
DR PDB; 1MFG; X-ray; 1.25 A; B=1247-1255.
DR PDB; 1MFL; X-ray; 1.88 A; B=1247-1255.
DR PDB; 1MW4; NMR; -; B=1135-1144.
DR PDB; 1N8Z; X-ray; 2.52 A; C=23-629.
DR PDB; 1QR1; X-ray; 2.40 A; C/F=654-662.
DR PDB; 1S78; X-ray; 3.25 A; A/B=23-646.
DR PDB; 2A91; X-ray; 2.50 A; A=22-530.
DR PDB; 2JWA; NMR; -; A/B=641-684.
DR PDB; 2KS1; NMR; -; A=641-684.
DR PDB; 2L4K; NMR; -; B=1135-1144.
DR PDB; 2N2A; NMR; -; A/B=644-700.
DR PDB; 3BE1; X-ray; 2.90 A; A=23-646.
DR PDB; 3H3B; X-ray; 2.45 A; A/B=23-214.
DR PDB; 3MZW; X-ray; 2.90 A; A=23-646.
DR PDB; 3N85; X-ray; 3.20 A; A=23-646.
DR PDB; 3PP0; X-ray; 2.25 A; A/B=703-1029.
DR PDB; 3RCD; X-ray; 3.21 A; A/B/C/D=713-1028.
DR PDB; 3WLW; X-ray; 3.09 A; A/B=23-586.
DR PDB; 3WSQ; X-ray; 3.50 A; A=23-586.
DR PDB; 4GFU; X-ray; 2.00 A; F=1246-1252.
DR PDB; 4HRL; X-ray; 2.55 A; C=24-219.
DR PDB; 4HRM; X-ray; 3.20 A; A/C=24-219.
DR PDB; 4HRN; X-ray; 2.65 A; C/D=529-625.
DR PDB; 4NND; X-ray; 2.50 A; C/E/F/H=1109-1114.
DR PDB; 5K33; X-ray; 3.30 A; C=23-629.
DR PDB; 5KWG; X-ray; 4.30 A; C=23-653.
DR PDB; 5MY6; X-ray; 2.25 A; A=24-645.
DR PDB; 5O4G; X-ray; 3.00 A; C=23-628.
DR PDB; 5OB4; NMR; -; A/B=641-684.
DR PDB; 5TQS; X-ray; 1.88 A; E/F/G/H=1218-1228.
DR PDB; 6ATT; X-ray; 3.77 A; A=23-652.
DR PDB; 6BGT; X-ray; 2.70 A; C=1-652.
DR PDB; 6J71; X-ray; 2.92 A; A=22-639.
DR PDB; 6LBX; X-ray; 2.03 A; B=531-626.
DR PDB; 6OGE; EM; 4.36 A; A=23-644.
DR PDB; 7JXH; X-ray; 3.27 A; A/B/C/D/E/F/G/H=703-1024.
DR PDB; 7MN5; EM; 2.93 A; B=1-1029.
DR PDB; 7MN6; EM; 3.09 A; B=1-1029.
DR PDB; 7MN8; EM; 3.45 A; B=1-1029.
DR PDBsum; 1MFG; -.
DR PDBsum; 1MFL; -.
DR PDBsum; 1MW4; -.
DR PDBsum; 1N8Z; -.
DR PDBsum; 1QR1; -.
DR PDBsum; 1S78; -.
DR PDBsum; 2A91; -.
DR PDBsum; 2JWA; -.
DR PDBsum; 2KS1; -.
DR PDBsum; 2L4K; -.
DR PDBsum; 2N2A; -.
DR PDBsum; 3BE1; -.
DR PDBsum; 3H3B; -.
DR PDBsum; 3MZW; -.
DR PDBsum; 3N85; -.
DR PDBsum; 3PP0; -.
DR PDBsum; 3RCD; -.
DR PDBsum; 3WLW; -.
DR PDBsum; 3WSQ; -.
DR PDBsum; 4GFU; -.
DR PDBsum; 4HRL; -.
DR PDBsum; 4HRM; -.
DR PDBsum; 4HRN; -.
DR PDBsum; 4NND; -.
DR PDBsum; 5K33; -.
DR PDBsum; 5KWG; -.
DR PDBsum; 5MY6; -.
DR PDBsum; 5O4G; -.
DR PDBsum; 5OB4; -.
DR PDBsum; 5TQS; -.
DR PDBsum; 6ATT; -.
DR PDBsum; 6BGT; -.
DR PDBsum; 6J71; -.
DR PDBsum; 6LBX; -.
DR PDBsum; 6OGE; -.
DR PDBsum; 7JXH; -.
DR PDBsum; 7MN5; -.
DR PDBsum; 7MN6; -.
DR PDBsum; 7MN8; -.
DR AlphaFoldDB; P04626; -.
DR BMRB; P04626; -.
DR SMR; P04626; -.
DR BioGRID; 108376; 490.
DR CORUM; P04626; -.
DR DIP; DIP-8N; -.
DR ELM; P04626; -.
DR IntAct; P04626; 404.
DR MINT; P04626; -.
DR STRING; 9606.ENSP00000269571; -.
DR BindingDB; P04626; -.
DR ChEMBL; CHEMBL1824; -.
DR DrugBank; DB08916; Afatinib.
DR DrugBank; DB06021; AV-412.
DR DrugBank; DB12267; Brigatinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB04988; IGN311.
DR DrugBank; DB01259; Lapatinib.
DR DrugBank; DB14967; Margetuximab.
DR DrugBank; DB06366; Pertuzumab.
DR DrugBank; DB11973; Tesevatinib.
DR DrugBank; DB00072; Trastuzumab.
DR DrugBank; DB05773; Trastuzumab emtansine.
DR DrugBank; DB11652; Tucatinib.
DR DrugBank; DB05944; Varlitinib.
DR DrugBank; DB15035; Zanubrutinib.
DR DrugCentral; P04626; -.
DR GuidetoPHARMACOLOGY; 2019; -.
DR MoonDB; P04626; Predicted.
DR TCDB; 8.A.23.1.39; the basigin (basigin) family.
DR CarbonylDB; P04626; -.
DR GlyConnect; 1710; 13 N-Linked glycans (5 sites), 1 O-Linked glycan (1 site).
DR GlyGen; P04626; 9 sites, 11 N-linked glycans (5 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; P04626; -.
DR PhosphoSitePlus; P04626; -.
DR SwissPalm; P04626; -.
DR BioMuta; ERBB2; -.
DR DMDM; 119533; -.
DR CPTAC; CPTAC-192; -.
DR CPTAC; CPTAC-193; -.
DR CPTAC; CPTAC-194; -.
DR CPTAC; CPTAC-195; -.
DR CPTAC; CPTAC-693; -.
DR EPD; P04626; -.
DR jPOST; P04626; -.
DR MassIVE; P04626; -.
DR MaxQB; P04626; -.
DR PaxDb; P04626; -.
DR PeptideAtlas; P04626; -.
DR PRIDE; P04626; -.
DR ProteomicsDB; 51718; -. [P04626-1]
DR ProteomicsDB; 51719; -. [P04626-2]
DR ProteomicsDB; 51720; -. [P04626-3]
DR ProteomicsDB; 51721; -. [P04626-4]
DR ABCD; P04626; 71 sequenced antibodies.
DR Antibodypedia; 740; 6121 antibodies from 61 providers.
DR CPTC; P04626; 4 antibodies.
DR DNASU; 2064; -.
DR Ensembl; ENST00000269571.10; ENSP00000269571.4; ENSG00000141736.14. [P04626-1]
DR Ensembl; ENST00000406381.6; ENSP00000385185.2; ENSG00000141736.14. [P04626-5]
DR Ensembl; ENST00000541774.5; ENSP00000446466.1; ENSG00000141736.14. [P04626-4]
DR Ensembl; ENST00000584601.5; ENSP00000462438.1; ENSG00000141736.14. [P04626-5]
DR GeneID; 2064; -.
DR KEGG; hsa:2064; -.
DR MANE-Select; ENST00000269571.10; ENSP00000269571.4; NM_004448.4; NP_004439.2.
DR UCSC; uc060esv.1; human. [P04626-1]
DR CTD; 2064; -.
DR DisGeNET; 2064; -.
DR GeneCards; ERBB2; -.
DR HGNC; HGNC:3430; ERBB2.
DR HPA; ENSG00000141736; Low tissue specificity.
DR MalaCards; ERBB2; -.
DR MIM; 137800; phenotype.
DR MIM; 164870; gene.
DR MIM; 167000; phenotype.
DR MIM; 211980; phenotype.
DR MIM; 613659; phenotype.
DR MIM; 619465; phenotype.
DR neXtProt; NX_P04626; -.
DR OpenTargets; ENSG00000141736; -.
DR Orphanet; 388; Hirschsprung disease.
DR PharmGKB; PA27844; -.
DR VEuPathDB; HostDB:ENSG00000141736; -.
DR eggNOG; KOG1025; Eukaryota.
DR GeneTree; ENSGT00940000158232; -.
DR InParanoid; P04626; -.
DR OMA; YVSDRHC; -.
DR OrthoDB; 81952at2759; -.
DR PhylomeDB; P04626; -.
DR TreeFam; TF106002; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P04626; -.
DR Reactome; R-HSA-1227986; Signaling by ERBB2.
DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-HSA-1251932; PLCG1 events in ERBB2 signaling.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1306955; GRB7 events in ERBB2 signaling.
DR Reactome; R-HSA-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR Reactome; R-HSA-1963640; GRB2 events in ERBB2 signaling.
DR Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6785631; ERBB2 Regulates Cell Motility.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-8847993; ERBB2 Activates PTK6 Signaling.
DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling.
DR Reactome; R-HSA-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors.
DR Reactome; R-HSA-9634285; Constitutive Signaling by Overexpressed ERBB2.
DR Reactome; R-HSA-9652282; Drug-mediated inhibition of ERBB2 signaling.
DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants.
DR Reactome; R-HSA-9665233; Resistance of ERBB2 KD mutants to trastuzumab.
DR Reactome; R-HSA-9665244; Resistance of ERBB2 KD mutants to sapitinib.
DR Reactome; R-HSA-9665245; Resistance of ERBB2 KD mutants to tesevatinib.
DR Reactome; R-HSA-9665246; Resistance of ERBB2 KD mutants to neratinib.
DR Reactome; R-HSA-9665247; Resistance of ERBB2 KD mutants to osimertinib.
DR Reactome; R-HSA-9665249; Resistance of ERBB2 KD mutants to afatinib.
DR Reactome; R-HSA-9665250; Resistance of ERBB2 KD mutants to AEE788.
DR Reactome; R-HSA-9665251; Resistance of ERBB2 KD mutants to lapatinib.
DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants.
DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants.
DR Reactome; R-HSA-9665737; Drug resistance in ERBB2 TMD/JMD mutants.
DR SignaLink; P04626; -.
DR SIGNOR; P04626; -.
DR BioGRID-ORCS; 2064; 91 hits in 1117 CRISPR screens.
DR ChiTaRS; ERBB2; human.
DR EvolutionaryTrace; P04626; -.
DR GeneWiki; HER2/neu; -.
DR GenomeRNAi; 2064; -.
DR Pharos; P04626; Tclin.
DR PRO; PR:P04626; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P04626; protein.
DR Bgee; ENSG00000141736; Expressed in lower esophagus mucosa and 184 other tissues.
DR ExpressionAtlas; P04626; baseline and differential.
DR Genevisible; P04626; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0009925; C:basal plasma membrane; IBA:GO_Central.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0038143; C:ERBB3:ERBB2 complex; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL.
DR GO; GO:0044214; C:spanning component of plasma membrane; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0001042; F:RNA polymerase I core binding; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:BHF-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:BHF-UCL.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; TAS:ProtInc.
DR GO; GO:0038134; P:ERBB2-EGFR signaling pathway; IDA:MGI.
DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; IEA:Ensembl.
DR GO; GO:0038135; P:ERBB2-ERBB4 signaling pathway; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0033080; P:immature T cell proliferation in thymus; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
DR GO; GO:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; IEA:Ensembl.
DR GO; GO:0007528; P:neuromuscular junction development; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0007422; P:peripheral nervous system development; IEA:Ensembl.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:BHF-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:BHF-UCL.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:BHF-UCL.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IDA:UniProtKB.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; IMP:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0045765; P:regulation of angiogenesis; NAS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0032886; P:regulation of microtubule-based process; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042060; P:wound healing; IDA:BHF-UCL.
DR CDD; cd00064; FU; 3.
DR DisProt; DP01484; -.
DR Gene3D; 3.80.20.20; -; 2.
DR IDEAL; IID00293; -.
DR InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR032778; GF_recep_IV.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF14843; GF_recep_IV; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PIRSF; PIRSF000619; TyrPK_EGF-R; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00261; FU; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative initiation; Alternative splicing;
KW ATP-binding; Cell membrane; Chromosomal rearrangement; Cytoplasm;
KW Disease variant; Disulfide bond; Endosome; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Signal; Transcription; Transcription regulation; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1255
FT /note="Receptor tyrosine-protein kinase erbB-2"
FT /id="PRO_0000016669"
FT TOPO_DOM 23..652
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 653..675
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 676..1255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 720..987
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 676..689
FT /note="Required for interaction with KPNB1 and EEA1"
FT /evidence="ECO:0000269|PubMed:16314522"
FT REGION 1035..1179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1195..1197
FT /note="Interaction with PIK3C2B"
FT /evidence="ECO:0000305"
FT REGION 1196..1255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 676..689
FT /note="Nuclear localization signal"
FT COMPBIAS 1142..1157
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 845
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 726..734
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 753
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 182
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1054
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1078
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06494"
FT MOD_RES 1083
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1112
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:27134172"
FT MOD_RES 1139
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:27134172"
FT MOD_RES 1151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1166
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1196
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:27134172"
FT MOD_RES 1248
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17554007,
FT ECO:0000269|PubMed:27134172, ECO:0007744|PubMed:17081983"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20696930,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3MZW"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0007744|PDB:1N8Z,
FT ECO:0007744|PDB:1S78, ECO:0007744|PDB:2A91,
FT ECO:0007744|PDB:3N85"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15093539,
FT ECO:0000269|PubMed:19299620, ECO:0000269|PubMed:20696930,
FT ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85"
FT CARBOHYD 530
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15093539,
FT ECO:0000269|PubMed:19299620, ECO:0007744|PDB:1S78"
FT CARBOHYD 571
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20696930,
FT ECO:0007744|PDB:3MZW"
FT CARBOHYD 629
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 26..53
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3H3B, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRL,
FT ECO:0007744|PDB:4HRM"
FT DISULFID 162..192
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3H3B, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRL,
FT ECO:0007744|PDB:4HRM"
FT DISULFID 195..204
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3H3B, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRL,
FT ECO:0007744|PDB:4HRM"
FT DISULFID 199..212
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3H3B, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRL,
FT ECO:0007744|PDB:4HRM"
FT DISULFID 220..227
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 224..235
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 236..244
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 240..252
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 255..264
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 268..295
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 299..311
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 315..331
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 334..338
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 342..367
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 475..504
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 511..520
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 515..528
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:2A91, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3MZW, ECO:0007744|PDB:3N85,
FT ECO:0007744|PDB:3WLW, ECO:0007744|PDB:3WSQ"
FT DISULFID 531..540
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:3BE1, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRN"
FT DISULFID 544..560
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:3BE1, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRN"
FT DISULFID 563..576
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:3BE1, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRN"
FT DISULFID 567..584
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:3BE1, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:3WLW,
FT ECO:0007744|PDB:3WSQ, ECO:0007744|PDB:4HRN"
FT DISULFID 587..596
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:1S78,
FT ECO:0007744|PDB:3BE1, ECO:0007744|PDB:3MZW,
FT ECO:0007744|PDB:3N85, ECO:0007744|PDB:4HRN"
FT DISULFID 600..623
FT /evidence="ECO:0007744|PDB:1N8Z, ECO:0007744|PDB:3BE1,
FT ECO:0007744|PDB:3N85"
FT DISULFID 626..634
FT /evidence="ECO:0007744|PDB:3N85"
FT DISULFID 630..642
FT /evidence="ECO:0007744|PDB:3N85"
FT VAR_SEQ 1..686
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_039250"
FT VAR_SEQ 1..610
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_039249"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_054787"
FT VAR_SEQ 1..23
FT /note="MELAALCRWGLLLALLPPGAAST -> MPRGSWKP (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_039248"
FT VAR_SEQ 633..648
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:24722188"
FT /id="VSP_055902"
FT VAR_SEQ 771..883
FT /note="AYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDL
FT LNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADG
FT GK -> TISNLFSNFAPRGPSACCEPTCWCHSGKGQDSLPREEWGRQRRFCLWGCRGEP
FT RVLDTPGRSCPSAPPSSCLQPSLRQPLLLGPGPTRAGGSTQHLQRDTYGREPRVPGSGR
FT ASVNQKAKSAEALMCPQGAGKA (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:24722188"
FT /id="VSP_055903"
FT VAR_SEQ 884..1255
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:24722188"
FT /id="VSP_055904"
FT VARIANT 452
FT /note="W -> C (in dbSNP:rs4252633)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016317"
FT VARIANT 654
FT /note="I -> V (in allele B3; dbSNP:rs1801201)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:8095488"
FT /id="VAR_004077"
FT VARIANT 655
FT /note="I -> V (in allele B2 and allele B3;
FT dbSNP:rs1136201)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:8095488, ECO:0000269|Ref.3"
FT /id="VAR_004078"
FT VARIANT 710
FT /note="A -> V (in VSCN2; almost complete loss of ERBB2 and
FT ERBB3 phosphorylation in the presence or in the absence of
FT NRG1 stimulation, suggesting alteration of downstream
FT signaling; does not affect the subcellular localization at
FT the cell membrane)"
FT /evidence="ECO:0000269|PubMed:33497358"
FT /id="VAR_086107"
FT VARIANT 755
FT /note="L -> P (in LNCR; somatic mutation; unknown
FT pathological significance; dbSNP:rs121913469)"
FT /evidence="ECO:0000269|PubMed:15457249"
FT /id="VAR_055432"
FT VARIANT 768
FT /note="L -> S (in dbSNP:rs56366519)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042097"
FT VARIANT 774
FT /note="M -> MAYVM (in LNCR; somatic mutation; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:15457249"
FT /id="VAR_055433"
FT VARIANT 776
FT /note="G -> S (in GASC; somatic mutation; unknown
FT pathological significance; dbSNP:rs28933369)"
FT /evidence="ECO:0000269|PubMed:15457249,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_042098"
FT VARIANT 779
FT /note="S -> SVGS (in LNCR; somatic mutation; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:15457249"
FT /id="VAR_055434"
FT VARIANT 857
FT /note="N -> S (in OC; somatic mutation; unknown
FT pathological significance; dbSNP:rs28933370)"
FT /evidence="ECO:0000269|PubMed:15457249,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_042099"
FT VARIANT 914
FT /note="E -> K (in GLM; somatic mutation; unknown
FT pathological significance; dbSNP:rs28933368)"
FT /evidence="ECO:0000269|PubMed:15457249"
FT /id="VAR_055435"
FT VARIANT 1170
FT /note="P -> A (in dbSNP:rs1058808)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:2999974, ECO:0000269|PubMed:8104414,
FT ECO:0000269|Ref.3"
FT /id="VAR_016318"
FT VARIANT 1216
FT /note="A -> D (in dbSNP:rs55943169)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042100"
FT MUTAGEN 317..318
FT /note="LH->AA: Reduces dimerization with ERBB3."
FT /evidence="ECO:0000269|PubMed:15093539"
FT MUTAGEN 611
FT /note="M->A: Prevents synthesis of isoform 2."
FT /evidence="ECO:0000269|PubMed:16794579"
FT MUTAGEN 687
FT /note="M->A: Prevents synthesis of isoform 3."
FT /evidence="ECO:0000269|PubMed:16794579"
FT MUTAGEN 706
FT /note="M->A: No effect on isoform production."
FT /evidence="ECO:0000269|PubMed:16794579"
FT MUTAGEN 712
FT /note="M->A: No effect on isoform production."
FT /evidence="ECO:0000269|PubMed:16794579"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 39..50
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 55..64
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:3H3B"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:5MY6"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:3H3B"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:3H3B"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:2A91"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:5MY6"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:3H3B"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:1N8Z"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:3H3B"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:1N8Z"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 240..248
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 251..260
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:5MY6"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:5MY6"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:6J71"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:1N8Z"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:3MZW"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:2A91"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:5MY6"
FT TURN 358..360
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 361..364
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 368..376
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 378..382
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 385..387
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 394..400
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 405..408
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 410..413
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 430..435
FT /evidence="ECO:0007829|PDB:3WLW"
FT TURN 438..440
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 441..447
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 463..469
FT /evidence="ECO:0007829|PDB:5MY6"
FT TURN 476..479
FT /evidence="ECO:0007829|PDB:7MN5"
FT HELIX 482..485
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 488..490
FT /evidence="ECO:0007829|PDB:6J71"
FT STRAND 493..499
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 501..506
FT /evidence="ECO:0007829|PDB:5MY6"
FT TURN 507..509
FT /evidence="ECO:0007829|PDB:3N85"
FT HELIX 516..518
FT /evidence="ECO:0007829|PDB:5MY6"
FT STRAND 520..524
FT /evidence="ECO:0007829|PDB:5MY6"
FT HELIX 525..527
FT /evidence="ECO:0007829|PDB:2A91"
FT STRAND 532..536
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 539..542
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 545..551
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 553..556
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 559..562
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 565..567
FT /evidence="ECO:0007829|PDB:3WSQ"
FT STRAND 571..573
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 575..580
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 583..592
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 595..599
FT /evidence="ECO:0007829|PDB:6LBX"
FT STRAND 602..604
FT /evidence="ECO:0007829|PDB:6J71"
FT STRAND 615..617
FT /evidence="ECO:0007829|PDB:1N8Z"
FT STRAND 621..625
FT /evidence="ECO:0007829|PDB:1N8Z"
FT STRAND 630..632
FT /evidence="ECO:0007829|PDB:6J71"
FT STRAND 635..637
FT /evidence="ECO:0007829|PDB:6J71"
FT HELIX 651..678
FT /evidence="ECO:0007829|PDB:2JWA"
FT HELIX 684..690
FT /evidence="ECO:0007829|PDB:2N2A"
FT HELIX 691..697
FT /evidence="ECO:0007829|PDB:2N2A"
FT HELIX 717..719
FT /evidence="ECO:0007829|PDB:3PP0"
FT STRAND 720..728
FT /evidence="ECO:0007829|PDB:3PP0"
FT STRAND 730..739
FT /evidence="ECO:0007829|PDB:3PP0"
FT STRAND 748..755
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 761..774
FT /evidence="ECO:0007829|PDB:3PP0"
FT STRAND 785..799
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 806..812
FT /evidence="ECO:0007829|PDB:3PP0"
FT TURN 814..816
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 819..838
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 848..850
FT /evidence="ECO:0007829|PDB:3PP0"
FT STRAND 851..855
FT /evidence="ECO:0007829|PDB:3PP0"
FT STRAND 858..861
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 886..888
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 891..896
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 901..916
FT /evidence="ECO:0007829|PDB:3PP0"
FT TURN 922..925
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 928..930
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 931..936
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 949..958
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 963..965
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 969..980
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 983..986
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 989..992
FT /evidence="ECO:0007829|PDB:3PP0"
FT HELIX 1003..1007
FT /evidence="ECO:0007829|PDB:3PP0"
FT STRAND 1140..1142
FT /evidence="ECO:0007829|PDB:1MW4"
SQ SEQUENCE 1255 AA; 137910 MW; 39E9DFDA04DCF962 CRC64;
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
