Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)]

 ERBB4_HUMAN             Reviewed;        1308 AA.
Q15303; B7ZLD7; B7ZLE2; B7ZLE3; Q2M1W1; Q59EW4;
15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
30-AUG-2017, entry version 197.
RecName: Full=Receptor tyrosine-protein kinase erbB-4;
EC=2.7.10.1;
AltName: Full=Proto-oncogene-like protein c-ErbB-4;
AltName: Full=Tyrosine kinase-type cell surface receptor HER4;
AltName: Full=p180erbB4;
Contains:
RecName: Full=ERBB4 intracellular domain;
Short=4ICD;
Short=E4ICD;
AltName: Full=s80HER4;
Flags: Precursor;
Name=ERBB4; Synonyms=HER4;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM JM-A CYT-1), FUNCTION AS CELL
SURFACE RECEPTOR, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND
TISSUE SPECIFICITY.
TISSUE=Mammary carcinoma;
PubMed=8383326; DOI=10.1073/pnas.90.5.1746;
Plowman G.D., Culouscou J.-M., Whitney G.S., Green J.M., Carlton G.W.,
Foy L., Neubauer M.G., Shoyab M.;
"Ligand-specific activation of HER4/p180erbB4, a fourth member of the
epidermal growth factor receptor family.";
Proc. Natl. Acad. Sci. U.S.A. 90:1746-1750(1993).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS JM-A CYT-1 AND JM-B CYT-1),
TISSUE SPECIFICITY, FUNCTION AS CELL SURFACE RECEPTOR FOR NRG1 AND
BTC, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, AND PROTEOLYTIC
PROCESSING.
TISSUE=Fetal brain;
PubMed=9334263; DOI=10.1074/jbc.272.42.26761;
Elenius K., Corfas G., Paul S., Choi C.J., Rio C., Plowman G.D.,
Klagsbrun M.;
"A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific
tissue distribution and differential processing in response to phorbol
ester.";
J. Biol. Chem. 272:26761-26768(1997).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS JM-A CYT-1; JM-B
CYT-1; JM-A CYT-2 AND JM-B CYT-2).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 401-1308 (ISOFORM JM-A
CYT-2).
TISSUE=Brain;
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
Ohara O., Nagase T., Kikuno R.F.;
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[5]
INTERACTION WITH NRG1, AND AUTOPHOSPHORYLATION.
PubMed=7689552;
Culouscou J.-M., Plowman G.D., Carlton G.W., Green J.M., Shoyab M.;
"Characterization of a breast cancer cell differentiation factor that
specifically activates the HER4/p180erbB4 receptor.";
J. Biol. Chem. 268:18407-18410(1993).
[6]
INTERACTION WITH NRG1, AND AUTOPHOSPHORYLATION.
PubMed=7902537; DOI=10.1038/366473a0;
Plowman G.D., Green J.M., Culouscou J.M., Carlton G.W., Rothwell V.M.,
Buckley S.;
"Heregulin induces tyrosine phosphorylation of HER4/p180erbB4.";
Nature 366:473-475(1993).
[7]
FUNCTION AS NRG1 RECEPTOR IN REGULATION OF CELL PROLIFERATION,
CATALYTIC ACTIVITY, ENZYME REGULATION, AUTOPHOSPHORYLATION,
PHOSPHORYLATION AT TYR-1056; TYR-1188 AND TYR-1242, AND INTERACTION
WITH EGFR; SHC1 AND PIK3R1.
PubMed=8617750; DOI=10.1074/jbc.271.9.4813;
Cohen B.D., Green J.M., Foy L., Fell H.P.;
"HER4-mediated biological and biochemical properties in NIH 3T3 cells.
Evidence for HER1-HER4 heterodimers.";
J. Biol. Chem. 271:4813-4818(1996).
[8]
INTERACTION WITH BTC, AND AUTOPHOSPHORYLATION.
PubMed=8570211;
Riese D.J. II, Bermingham Y., van Raaij T.M., Buckley S.,
Plowman G.D., Stern D.F.;
"Betacellulin activates the epidermal growth factor receptor and erbB-
4, and induces cellular response patterns distinct from those
stimulated by epidermal growth factor or neuregulin-beta.";
Oncogene 12:345-353(1996).
[9]
FUNCTION AS HBEGF RECEPTOR; IN CELL MIGRATION; CELL PROLIFERATION AND
IN ACTIVATION OF PIK3R1, INTERACTION WITH HBEGF AND PIK3R1, AND
AUTOPHOSPHORYLATION.
PubMed=9135143; DOI=10.1093/emboj/16.6.1268;
Elenius K., Paul S., Allison G., Sun J., Klagsbrun M.;
"Activation of HER4 by heparin-binding EGF-like growth factor
stimulates chemotaxis but not proliferation.";
EMBO J. 16:1268-1278(1997).
[10]
INTERACTION WITH NRG2, FUNCTION AS NRG2 RECEPTOR, AND PHOSPHORYLATION.
PubMed=9168115; DOI=10.1038/387512a0;
Carraway K.L. III, Weber J.L., Unger M.J., Ledesma J., Yu N.,
Gassmann M., Lai C.;
"Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine
kinases.";
Nature 387:512-516(1997).
[11]
INTERACTION WITH EREG, AND AUTOPHOSPHORYLATION.
PubMed=9419975; DOI=10.1038/sj.onc.1201458;
Komurasaki T., Toyoda H., Uchida D., Morimoto S.;
"Epiregulin binds to epidermal growth factor receptor and ErbB-4 and
induces tyrosine phosphorylation of epidermal growth factor receptor,
ErbB-2, ErbB-3 and ErbB-4.";
Oncogene 15:2841-2848(1997).
[12]
INTERACTION WITH NRG3, AND AUTOPHOSPHORYLATION.
PubMed=9275162; DOI=10.1073/pnas.94.18.9562;
Zhang D., Sliwkowski M.X., Mark M., Frantz G., Akita R., Sun Y.,
Hillan K., Crowley C., Brush J., Godowski P.J.;
"Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that
binds and activates ErbB4.";
Proc. Natl. Acad. Sci. U.S.A. 94:9562-9567(1997).
[13]
INTERACTION WITH GRB7.
PubMed=9516479; DOI=10.1074/jbc.273.13.7717;
Fiddes R.J., Campbell D.H., Janes P.W., Sivertsen S.P., Sasaki H.,
Wallasch C., Daly R.J.;
"Analysis of Grb7 recruitment by heregulin-activated erbB receptors
reveals a novel target selectivity for erbB3.";
J. Biol. Chem. 273:7717-7724(1998).
[14]
INTERACTION WITH ERBB2, AND FUNCTION IN ACTIVATION OF STAT5A.
PubMed=10358079; DOI=10.1074/jbc.274.24.17209;
Olayioye M.A., Beuvink I., Horsch K., Daly J.M., Hynes N.E.;
"ErbB receptor-induced activation of stat transcription factors is
mediated by Src tyrosine kinases.";
J. Biol. Chem. 274:17209-17218(1999).
[15]
ALTERNATIVE SPLICING, FUNCTION IN PHOSPHORYLATION AND ACTIVATION OF
PIK3R1, INTERACTION WITH NRG1 AND PIKR3R1, AUTOPHOSPHORYLATION, AND
TISSUE SPECIFICITY.
PubMed=10353604; DOI=10.1038/sj.onc.1202612;
Elenius K., Choi C.J., Paul S., Santiestevan E., Nishi E.,
Klagsbrun M.;
"Characterization of a naturally occurring ErbB4 isoform that does not
bind or activate phosphatidyl inositol 3-kinase.";
Oncogene 18:2607-2615(1999).
[16]
FUNCTION AS NRG4 RECEPTOR IN ACTIVATION OF MAPK1/ERK2 AND MAPK3/ERK1
AND IN CELL PROLIFERATION, INTERACTION WITH NRG4, AND SUBCELLULAR
LOCATION.
PubMed=10348342; DOI=10.1038/sj.onc.1202631;
Harari D., Tzahar E., Romano J., Shelly M., Pierce J.H., Andrews G.C.,
Yarden Y.;
"Neuregulin-4: a novel growth factor that acts through the ErbB-4
receptor tyrosine kinase.";
Oncogene 18:2681-2689(1999).
[17]
FUNCTION AS NRG1 RECEPTOR IN CELL PROLIFERATION; MIGRATION; SURVIVAL
AND IN PHOSPHORYLATION OF SHC1; ACTIVATION OF MAPK1/ERK2 AND
MAPK3/ERK1, AND ALTERNATIVE SPLICING.
PubMed=10722704; DOI=10.1074/jbc.275.12.8641;
Kainulainen V., Sundvall M., Maatta J.A., Santiestevan E.,
Klagsbrun M., Elenius K.;
"A natural ErbB4 isoform that does not activate phosphoinositide 3-
kinase mediates proliferation but not survival or chemotaxis.";
J. Biol. Chem. 275:8641-8649(2000).
[18]
PROTEOLYTIC PROCESSING.
PubMed=10744726; DOI=10.1074/jbc.275.14.10379;
Rio C., Buxbaum J.D., Peschon J.J., Corfas G.;
"Tumor necrosis factor-alpha-converting enzyme is required for
cleavage of erbB4/HER4.";
J. Biol. Chem. 275:10379-10387(2000).
[19]
FUNCTION IN ACTIVATION OF AKT1; MAPK1/ERK2 AND MAPK3/ERK1, INTERACTION
WITH PIK3R1; GRB2; SHC1; BTC; NRG1; NRG2 AND NRG3, AND LIGAND-SPECIFIC
AUTOPHOSPHORYLATION.
PubMed=10867024; DOI=10.1074/jbc.C901015199;
Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C.,
Carraway K.L. III;
"Ligand discrimination in signaling through an ErbB4 receptor
homodimer.";
J. Biol. Chem. 275:19803-19807(2000).
[20]
INTERACTION WITH DLG2; DLG3; DLG4 AND SNTB2.
PubMed=10725395; DOI=10.1073/pnas.97.7.3596;
Garcia R.A., Vasudevan K., Buonanno A.;
"The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins
at neuronal synapses.";
Proc. Natl. Acad. Sci. U.S.A. 97:3596-3601(2000).
[21]
FUNCTION AS NRG1 RECEPTOR AND IN ACTIVATION OF MAP KINASES,
AUTOPHOSPHORYLATION, AND ENZYME REGULATION.
PubMed=11178955; DOI=10.1006/bbrc.2001.4302;
Egeblad M., Mortensen O.H., van Kempen L.C., Jaattela M.;
"BIBX1382BS, but not AG1478 or PD153035, inhibits the ErbB kinases at
different concentrations in intact cells.";
Biochem. Biophys. Res. Commun. 281:25-31(2001).
[22]
MUTAGENESIS OF LYS-751, AND FUNCTION IN PROMOTING CELL DIFFERENTIATION
AND INHIBITING CELL PROLIFERATION.
PubMed=11390655; DOI=10.1128/MCB.21.13.4265-4275.2001;
Sartor C.I., Zhou H., Kozlowska E., Guttridge K., Kawata E.,
Caskey L., Harrelson J., Hynes N., Ethier S., Calvo B., Earp H.S. III;
"Her4 mediates ligand-dependent antiproliferative and differentiation
responses in human breast cancer cells.";
Mol. Cell. Biol. 21:4265-4275(2001).
[23]
FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, INTERACTION
WITH YAP1, AND MUTAGENESIS OF TYR-1301.
PubMed=12807903; DOI=10.1074/jbc.M305597200;
Komuro A., Nagai M., Navin N.E., Sudol M.;
"WW domain-containing protein YAP associates with ErbB-4 and acts as a
co-transcriptional activator for the carboxyl-terminal fragment of
ErbB-4 that translocates to the nucleus.";
J. Biol. Chem. 278:33334-33341(2003).
[24]
INTERACTION WITH MUC1.
PubMed=12939402;
Li Y., Yu W.-H., Ren J., Chen W., Huang L., Kharbanda S., Loda M.,
Kufe D.;
"Heregulin targets gamma-catenin to the nucleolus by a mechanism
dependent on the DF3/MUC1 oncoprotein.";
Mol. Cancer Res. 1:765-775(2003).
[25]
INTERACTION WITH STAT5A, SUBCELLULAR LOCATION, FUNCTION IN NUCLEAR
LOCALIZATION OF STAT5A; DNA-BINDING, AND MUTAGENESIS OF
681-LYS--ARG-684.
PubMed=15534001; DOI=10.1083/jcb.200403155;
Williams C.C., Allison J.G., Vidal G.A., Burow M.E., Beckman B.S.,
Marrero L., Jones F.E.;
"The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by
functioning as a STAT5A nuclear chaperone.";
J. Cell Biol. 167:469-478(2004).
[26]
INTERACTION WITH WWOX, DOMAIN, AND MUTAGENESIS OF TYR-1035 AND
TYR-1301.
PubMed=16061658; DOI=10.1158/0008-5472.CAN-05-1150;
Aqeilan R.I., Donati V., Palamarchuk A., Trapasso F., Kaou M.,
Pekarsky Y., Sudol M., Croce C.M.;
"WW domain-containing proteins, WWOX and YAP, compete for interaction
with ErbB-4 and modulate its transcriptional function.";
Cancer Res. 65:6764-6772(2005).
[27]
FUNCTION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF VAL-675.
PubMed=15746097; DOI=10.1074/jbc.M412457200;
Vidal G.A., Naresh A., Marrero L., Jones F.E.;
"Presenilin-dependent gamma-secretase processing regulates multiple
ERBB4/HER4 activities.";
J. Biol. Chem. 280:19777-19783(2005).
[28]
FUNCTION IN PROMOTING APOPTOSIS, SUBCELLULAR LOCATION, AND INTERACTION
WITH BCL2.
PubMed=16778220; DOI=10.1158/0008-5472.CAN-05-2368;
Naresh A., Long W., Vidal G.A., Wimley W.C., Marrero L., Sartor C.I.,
Tovey S., Cooke T.G., Bartlett J.M., Jones F.E.;
"The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein
promoting apoptosis of breast cancer cells.";
Cancer Res. 66:6412-6420(2006).
[29]
INTERACTION WITH CBFA2T3.
PubMed=16815842; DOI=10.1074/jbc.M603998200;
Linggi B., Carpenter G.;
"ErbB-4 s80 intracellular domain abrogates ETO2-dependent
transcriptional repression.";
J. Biol. Chem. 281:25373-25380(2006).
[30]
FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
PubMed=16251361; DOI=10.1091/mbc.E05-05-0402;
Maatta J.A., Sundvall M., Junttila T.T., Peri L., Laine V.J.,
Isola J., Egeblad M., Elenius K.;
"Proteolytic cleavage and phosphorylation of a tumor-associated ErbB4
isoform promote ligand-independent survival and cancer cell growth.";
Mol. Biol. Cell 17:67-79(2006).
[31]
FUNCTION IN DIFFERENTIATION OF MAMMARY EPITHELIUM, PROTEOLYTIC
PROCESSING, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION
WITH STAT5A.
PubMed=16837552; DOI=10.1091/mbc.E06-02-0101;
Muraoka-Cook R.S., Sandahl M., Husted C., Hunter D., Miraglia L.,
Feng S.M., Elenius K., Earp H.S. III;
"The intracellular domain of ErbB4 induces differentiation of mammary
epithelial cells.";
Mol. Biol. Cell 17:4118-4129(2006).
[32]
MUTAGENESIS OF GLN-646, AND PHOSPHORYLATION AT TYR-1056.
PubMed=17120616;
Pitfield S.E., Bryant I., Penington D.J., Park G., Riese D.J. II;
"Phosphorylation of ErbB4 on tyrosine 1056 is critical for ErbB4
coupling to inhibition of colony formation by human mammary cell
lines.";
Oncol. Res. 16:179-193(2006).
[33]
FUNCTION OF ERBB4 INTRACELLULAR DOMAIN, PROTEOLYTIC PROCESSING,
SUBCELLULAR LOCATION, UBIQUITINATION OF ERBB4 INTRACELLULAR DOMAIN,
AND MUTAGENESIS OF VAL-675; LYS-751; ARG-992; LEU-995 AND ASP-1000.
PubMed=17638867; DOI=10.1158/0008-5472.CAN-06-4145;
Strunk K.E., Husted C., Miraglia L.C., Sandahl M., Rearick W.A.,
Hunter D.M., Earp H.S. III, Muraoka-Cook R.S.;
"HER4 D-box sequences regulate mitotic progression and degradation of
the nuclear HER4 cleavage product s80HER4.";
Cancer Res. 67:6582-6590(2007).
[34]
INTERACTION WITH ERBB2, MUTAGENESIS OF ASP-843, AND
AUTOPHOSPHORYLATION IN TRANS.
PubMed=16978839; DOI=10.1016/j.cellsig.2006.07.020;
Li Z., Mei Y., Liu X., Zhou M.;
"Neuregulin-1 only induces trans-phosphorylation between ErbB receptor
heterodimer partners.";
Cell. Signal. 19:466-471(2007).
[35]
FUNCTION OF E4ICD, PHOSPHORYLATION, SUBCELLULAR LOCATION OF E4ICD, AND
MUTAGENESIS OF LYS-751.
PubMed=17486069; DOI=10.1038/sj.onc.1210501;
Sundvall M., Peri L., Maatta J.A., Tvorogov D., Paatero I.,
Savisalo M., Silvennoinen O., Yarden Y., Elenius K.;
"Differential nuclear localization and kinase activity of alternative
ErbB4 intracellular domains.";
Oncogene 26:6905-6914(2007).
[36]
PHOSPHORYLATION AT TYR-875; TYR-1035; TYR-1056; TYR-1150; TYR-1162;
TYR-1188; TYR-1202; TYR-1242; TYR-1258 AND TYR-1284, INTERACTION WITH
PIK3R1 AND STAT1, AND IDENTIFICATION BY MASS SPECTROMETRY.
PubMed=18721752; DOI=10.1016/j.chembiol.2008.07.006;
Kaushansky A., Gordus A., Budnik B.A., Lane W.S., Rush J.,
MacBeath G.;
"System-wide investigation of ErbB4 reveals 19 sites of Tyr
phosphorylation that are unusually selective in their recruitment
properties.";
Chem. Biol. 15:808-817(2008).
[37]
INTERACTION WITH NEDD4, SUBCELLULAR LOCATION, AND UBIQUITINATION OF
E4ICD1.
PubMed=19193720; DOI=10.1096/fj.08-121947;
Zeng F., Xu J., Harris R.C.;
"Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in
MDCK II cells.";
FASEB J. 23:1935-1945(2009).
[38]
FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS, INTERACTION WITH ERBB2,
CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, PHOSPHORYLATION BY ERBB2,
ENZYME REGULATION, AND MUTAGENESIS OF VAL-721; ALA-773; ARG-782;
GLU-810; PRO-854; ASP-861; GLU-872 AND THR-926.
PubMed=19098003; DOI=10.1074/jbc.M805438200;
Tvorogov D., Sundvall M., Kurppa K., Hollmen M., Repo S.,
Johnson M.S., Elenius K.;
"Somatic mutations of ErbB4: selective loss-of-function phenotype
affecting signal transduction pathways in cancer.";
J. Biol. Chem. 284:5582-5591(2009).
[39]
INTERACTION WITH WWP1, AND MUTAGENESIS OF TYR-1056 AND TYR-1301.
PubMed=19561640; DOI=10.1038/onc.2009.162;
Li Y., Zhou Z., Alimandi M., Chen C.;
"WW domain containing E3 ubiquitin protein ligase 1 targets the full-
length ErbB4 for ubiquitin-mediated degradation in breast cancer.";
Oncogene 28:2948-2958(2009).
[40]
INTERACTION WITH TXNL4A; DDX23; MATR3; RBM15; ILF3; TRIM28; U5S1;
U2SURP; ITCH; HNRPU; AP2A1; NULC; LEO1; WWP2; MDM2; HXK1 AND ARS2,
FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
SPECTROMETRY.
PubMed=20858735; DOI=10.1158/1541-7786.MCR-10-0042;
Gilmore-Hebert M., Ramabhadran R., Stern D.F.;
"Interactions of ErbB4 and Kap1 connect the growth factor and DNA
damage response pathways.";
Mol. Cancer Res. 8:1388-1398(2010).
[41]
ENZYME REGULATION.
PubMed=21439954; DOI=10.1016/j.yexcr.2011.03.015;
Carrasco-Garcia E., Saceda M., Grasso S., Rocamora-Reverte L.,
Conde M., Gomez-Martinez A., Garcia-Morales P., Ferragut J.A.,
Martinez-Lacaci I.;
"Small tyrosine kinase inhibitors interrupt EGFR signaling by
interacting with erbB3 and erbB4 in glioblastoma cell lines.";
Exp. Cell Res. 317:1476-1489(2011).
[42]
REVIEW ON ROLE IN BREAST AND NEURAL DEVELOPMENT.
PubMed=14504474;
Jones F.E., Golding J.P., Gassmann M.;
"ErbB4 signaling during breast and neural development: novel genetic
models reveal unique ErbB4 activities.";
Cell Cycle 2:555-559(2003).
[43]
REVIEW.
PubMed=15944951;
Zaczek A., Brandt B., Bielawski K.P.;
"The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine
kinase receptors and the consequences for therapeutic approaches.";
Histol. Histopathol. 20:1005-1015(2005).
[44]
REVIEW ON ROLE IN MAMMARY GLAND DEVELOPMENT.
PubMed=18437540; DOI=10.1007/s10911-008-9080-x;
Muraoka-Cook R.S., Feng S.M., Strunk K.E., Earp H.S. III;
"ErbB4/HER4: role in mammary gland development, differentiation and
growth inhibition.";
J. Mammary Gland Biol. Neoplasia 13:235-246(2008).
[45]
REVIEW ON ROLE OF THE ERBB4 INTRACELLULAR DOMAIN.
PubMed=18473151; DOI=10.1007/s10911-008-9076-6;
Jones F.E.;
"HER4 intracellular domain (4ICD) activity in the developing mammary
gland and breast cancer.";
J. Mammary Gland Biol. Neoplasia 13:247-258(2008).
[46]
REVIEW ON LIGAND SPECIFICITY AND SIGNALING.
PubMed=18454307; DOI=10.1007/s10911-008-9079-3;
Sundvall M., Iljin K., Kilpinen S., Sara H., Kallioniemi O.P.,
Elenius K.;
"Role of ErbB4 in breast cancer.";
J. Mammary Gland Biol. Neoplasia 13:259-268(2008).
[47]
REVIEW ON ROLE IN NRG1 SIGNALING AND CARDIOVASCULAR HEALTH.
PubMed=20933198; DOI=10.1016/S1054-3589(10)59002-1;
Xu Y., Li X., Liu X., Zhou M.;
"Neuregulin-1/ErbB signaling and chronic heart failure.";
Adv. Pharmacol. 59:31-51(2010).
[48]
REVIEW ON ALTERNATIVE SPLICING AND PROTEOLYTIC PROCESSING; TISSUE
SPECIFICITY; SIGNALING AND ROLE IN DISEASE.
PubMed=21811097; DOI=10.4161/cc.10.16.17194;
Veikkolainen V., Vaparanta K., Halkilahti K., Iljin K., Sundvall M.,
Elenius K.;
"Function of ERBB4 is determined by alternative splicing.";
Cell Cycle 10:2647-2657(2011).
[49]
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 26-641, DISULFIDE BONDS, AND
GLYCOSYLATION AT ASN-138; ASN-174; ASN-253; ASN-358; ASN-410; ASN-473;
ASN-495 AND ASN-576.
PubMed=16203964; DOI=10.1073/pnas.0507591102;
Bouyain S., Longo P.A., Li S., Ferguson K.M., Leahy D.J.;
"The extracellular region of ErbB4 adopts a tethered conformation in
the absence of ligand.";
Proc. Natl. Acad. Sci. U.S.A. 102:15024-15029(2005).
[50]
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 690-999 IN COMPLEX WITH
INHIBITOR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
LEU-710; MET-766; LEU-864 AND ILE-947.
PubMed=18287036; DOI=10.1073/pnas.0708281105;
Wood E.R., Shewchuk L.M., Ellis B., Brignola P., Brashear R.L.,
Caferro T.R., Dickerson S.H., Dickson H.D., Donaldson K.H., Gaul M.,
Griffin R.J., Hassell A.M., Keith B., Mullin R., Petrov K.G.,
Reno M.J., Rusnak D.W., Tadepalli S.M., Ulrich J.C., Wagner C.D.,
Vanderwall D.E., Waterson A.G., Williams J.D., White W.L.,
Uehling D.E.;
"6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-
anilines as tunable covalent modifiers of ErbB kinases.";
Proc. Natl. Acad. Sci. U.S.A. 105:2773-2778(2008).
[51]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 702-1029 OF APOPROTEIN AND IN
COMPLEX WITH LAPATINIB, CATALYTIC ACTIVITY, ENZYME REGULATION,
AUTOPHOSPHORYLATION, AND SUBUNIT.
PubMed=18334220; DOI=10.1016/j.str.2007.12.016;
Qiu C., Tarrant M.K., Choi S.H., Sathyamurthy A., Bose R., Banjade S.,
Pal A., Bornmann W.G., Lemmon M.A., Cole P.A., Leahy D.J.;
"Mechanism of activation and inhibition of the HER4/ErbB4 kinase.";
Structure 16:460-467(2008).
[52]
VARIANTS [LARGE SCALE ANALYSIS] ILE-140 AND TYR-303.
PubMed=17344846; DOI=10.1038/nature05610;
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
[53]
VARIANTS ALS19 GLN-927 AND TRP-1275, AND CHARACTERIZATION OF VARIANTS
ASL19 GLN-927 AND TRP-1275.
PubMed=24119685; DOI=10.1016/j.ajhg.2013.09.008;
Takahashi Y., Fukuda Y., Yoshimura J., Toyoda A., Kurppa K.,
Moritoyo H., Belzil V.V., Dion P.A., Higasa K., Doi K., Ishiura H.,
Mitsui J., Date H., Ahsan B., Matsukawa T., Ichikawa Y., Moritoyo T.,
Ikoma M., Hashimoto T., Kimura F., Murayama S., Onodera O.,
Nishizawa M., Yoshida M., Atsuta N., Sobue G., Fifita J.A.,
Williams K.L., Blair I.P., Nicholson G.A., Gonzalez-Perez P.,
Brown R.H. Jr., Nomoto M., Elenius K., Rouleau G.A., Fujiyama A.,
Morishita S., Goto J., Tsuji S., Nakamura R., Watanabe H., Izumi Y.,
Kaji R., Morita M., Ogaki K., Taniguchi A., Aiba I., Mizoguchi K.,
Okamoto K., Hasegawa K., Aoki M., Kawata A., Nakano I., Abe K.,
Oda M., Konagaya M., Imai T., Nakagawa M., Fujita T., Sasaki H.,
Nishizawa M.;
"ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause
amyotrophic lateral sclerosis type 19.";
Am. J. Hum. Genet. 93:900-905(2013).
-!- FUNCTION: Tyrosine-protein kinase that plays an essential role as
cell surface receptor for neuregulins and EGF family members and
regulates development of the heart, the central nervous system and
the mammary gland, gene transcription, cell proliferation,
differentiation, migration and apoptosis. Required for normal
cardiac muscle differentiation during embryonic development, and
for postnatal cardiomyocyte proliferation. Required for normal
development of the embryonic central nervous system, especially
for normal neural crest cell migration and normal axon guidance.
Required for mammary gland differentiation, induction of milk
proteins and lactation. Acts as cell-surface receptor for the
neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members
BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization
and autophosphorylation at specific tyrosine residues that then
serve as binding sites for scaffold proteins and effectors. Ligand
specificity and signaling is modulated by alternative splicing,
proteolytic processing, and by the formation of heterodimers with
other ERBB family members, thereby creating multiple combinations
of intracellular phosphotyrosines that trigger ligand- and
context-specific cellular responses. Mediates phosphorylation of
SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1.
Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1,
leading to the activation of phosphatidylinositol 3-kinase and
AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and
isoform JM-B CYT-1 mediate reorganization of the actin
cytoskeleton and promote cell migration in response to NRG1.
Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine
that mediates interaction with PIK3R1, and hence do not
phosphorylate PIK3R1, do not protect cells against apoptosis, and
do not promote reorganization of the actin cytoskeleton and cell
migration. Proteolytic processing of isoform JM-A CYT-1 and
isoform JM-A CYT-2 gives rise to the corresponding soluble
intracellular domains (4ICD) that translocate to the nucleus,
promote nuclear import of STAT5A, activation of STAT5A, mammary
epithelium differentiation, cell proliferation and activation of
gene expression. The ERBB4 soluble intracellular domains (4ICD)
colocalize with STAT5A at the CSN2 promoter to regulate
transcription of milk proteins during lactation. The ERBB4 soluble
intracellular domains can also translocate to mitochondria and
promote apoptosis. {ECO:0000269|PubMed:10348342,
ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079,
ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024,
ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655,
ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001,
ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361,
ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552,
ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867,
ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735,
ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750,
ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115,
ECO:0000269|PubMed:9334263}.
-!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
[protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE-
ProRule:PRU10028, ECO:0000269|PubMed:18287036,
ECO:0000269|PubMed:18334220, ECO:0000269|PubMed:19098003,
ECO:0000269|PubMed:8617750}.
-!- ENZYME REGULATION: Binding of a cognate ligand leads to
dimerization and activation by autophosphorylation on tyrosine
residues. In vitro kinase activity is increased by Mg(2+).
Inhibited by PD153035, lapatinib, gefitinib (iressa, ZD1839),
AG1478 and BIBX1382BS. {ECO:0000269|PubMed:11178955,
ECO:0000269|PubMed:18334220, ECO:0000269|PubMed:19098003,
ECO:0000269|PubMed:21439954, ECO:0000269|PubMed:8617750}.
-!- SUBUNIT: Monomer in the absence of bound ligand. Homodimer or
heterodimer with another ERBB family member upon ligand binding,
thus forming heterotetramers. Interacts with EGFR and ERBB2.
Interacts with CBFA2T3 (By similarity). Interacts with DLG2 (via
its PDZ domain), DLG3 (via its PDZ domain), DLG4 (via its PDZ
domain) and SNTB2 (via its PDZ domain). Interacts with MUC1.
Interacts (via its PPxy motifs) with WWOX. Interacts (via the PPxY
motif 3 of isoform JM-A CYT-2) with YAP1 (via the WW domain 1 of
isoform 1). Interacts (isoform JM-A CYT-1 and isoform JM-B CYT-1)
with WWP1. Interacts (via its intracellular domain) with TRIM28.
Interacts (via the intracellular domains of both CYT-1 and CYT-2
isoforms) with KAP1; the interaction does not phosphorylate KAP1
but represses ERBB4-mediated transcriptional activity. Interacts
with PRPU, DDX23, MATR3, RBM15, ILF3, KAP1, U5S1, U2SURP, ITCH,
HNRPU, AP2A1, NULC, LEO1, WWP2, IGHG1, HXK1, GRB7 AND ARS2.
Interacts (phosphorylated isoform JM-A CYT-1 and isoform JM-B CYT-
1) with PIK3R1. Interacts with SHC1. Interacts with GRB2.
Interacts (soluble intracellular domain) with STAT5A. Interacts
(soluble intracellular domain) with BCL2. Interacts
(phosphorylated) with STAT1. {ECO:0000250,
ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604,
ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10725395,
ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:12807903,
ECO:0000269|PubMed:12939402, ECO:0000269|PubMed:15534001,
ECO:0000269|PubMed:16061658, ECO:0000269|PubMed:16778220,
ECO:0000269|PubMed:16815842, ECO:0000269|PubMed:16837552,
ECO:0000269|PubMed:16978839, ECO:0000269|PubMed:18287036,
ECO:0000269|PubMed:18334220, ECO:0000269|PubMed:18721752,
ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:19193720,
ECO:0000269|PubMed:19561640, ECO:0000269|PubMed:20858735,
ECO:0000269|PubMed:7689552, ECO:0000269|PubMed:7902537,
ECO:0000269|PubMed:8570211, ECO:0000269|PubMed:8617750,
ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115,
ECO:0000269|PubMed:9275162, ECO:0000269|PubMed:9419975,
ECO:0000269|PubMed:9516479}.
-!- INTERACTION:
P42684:ABL2; NbExp=4; IntAct=EBI-80371, EBI-1102694;
P78352:DLG4; NbExp=6; IntAct=EBI-80371, EBI-80389;
P00533:EGFR; NbExp=2; IntAct=EBI-80371, EBI-297353;
P04626:ERBB2; NbExp=3; IntAct=EBI-80371, EBI-641062;
P21860:ERBB3; NbExp=4; IntAct=EBI-80371, EBI-720706;
P08238:HSP90AB1; NbExp=2; IntAct=EBI-80371, EBI-352572;
P29353:SHC1; NbExp=2; IntAct=EBI-80371, EBI-78835;
P46937:YAP1; NbExp=3; IntAct=EBI-80371, EBI-1044059;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10348342,
ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001,
ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220,
ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069,
ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19193720,
ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326,
ECO:0000269|PubMed:9334263}; Single-pass type I membrane protein
{ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:12807903,
ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:16251361,
ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552,
ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867,
ECO:0000269|PubMed:19193720, ECO:0000269|PubMed:20858735,
ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:9334263}. Note=In
response to NRG1 treatment, the activated receptor is
internalized.
-!- SUBCELLULAR LOCATION: ERBB4 intracellular domain: Nucleus
{ECO:0000269|PubMed:17486069}. Mitochondrion
{ECO:0000269|PubMed:17486069}. Note=Following proteolytical
processing E4ICD (E4ICD1 or E4ICD2 generated from the respective
isoforms) is translocated to the nucleus. Significantly more
E4ICD2 than E4ICD1 is found in the nucleus. E4ICD2 colocalizes
with YAP1 in the nucleus.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Name=JM-A CYT-1;
IsoId=Q15303-1; Sequence=Displayed;
Note=Proteolytical processing generates E4ICD1 (s80Cyt1).;
Name=JM-B CYT-1;
IsoId=Q15303-2; Sequence=VSP_002895;
Name=JM-A CYT-2;
IsoId=Q15303-3; Sequence=VSP_022148;
Note=Proteolytical processing generates E4ICD2 (s80Cyt2).;
Name=JM-B CYT-2;
IsoId=Q15303-4; Sequence=VSP_002895, VSP_022148;
-!- TISSUE SPECIFICITY: Expressed at highest levels in brain, heart,
kidney, in addition to skeletal muscle, parathyroid, cerebellum,
pituitary, spleen, testis and breast. Lower levels in thymus,
lung, salivary gland, and pancreas. Isoform JM-A CYT-1 and isoform
JM-B CYT-1 are expressed in cerebellum, but only the isoform JM-B
is expressed in the heart. {ECO:0000269|PubMed:10353604,
ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:9334263}.
-!- PTM: Isoform JM-A CYT-1 and isoform JM-A CYT-2 are processed by
ADAM17. Proteolytic processing in response to ligand or 12-O-
tetradecanoylphorbol-13-acetate stimulation results in the
production of 120 kDa soluble receptor forms and intermediate
membrane-anchored 80 kDa fragments (m80HER4), which are further
processed by a presenilin-dependent gamma-secretase to release a
cytoplasmic intracellular domain (E4ICD; E4ICD1/s80Cyt1 or
E4ICD2/s80Cyt2, depending on the isoform). Membrane-anchored 80
kDa fragments of the processed isoform JM-A CYT-1 are more readily
degraded by the proteasome than fragments of isoform JM-A CYT-2,
suggesting a prevalence of E4ICD2 over E4ICD1. Isoform JM-B CYT-1
and isoform JM-B CYT-2 lack the ADAM17 cleavage site and are not
processed by ADAM17, precluding further processing by gamma-
secretase. {ECO:0000269|PubMed:10744726,
ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15746097,
ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17638867,
ECO:0000269|PubMed:9334263}.
-!- PTM: Autophosphorylated on tyrosine residues in response to ligand
binding. Autophosphorylation occurs in trans, i.e. one subunit of
the dimeric receptor phosphorylates tyrosine residues on the other
subunit. Ligands trigger phosphorylation at specific tyrosine
residues, thereby creating binding sites for scaffold proteins and
effectors. Constitutively phosphorylated at a basal level when
overexpressed in heterologous systems; ligand binding leads to
increased phosphorylation. Phosphorylation at Tyr-1035 is
important for interaction with STAT1. Phosphorylation at Tyr-1056
is important for interaction with PIK3R1. Phosphorylation at Tyr-
1242 is important for interaction with SHC1. Phosphorylation at
Tyr-1188 may also contribute to the interaction with SHC1. Isoform
JM-A CYT-2 is constitutively phosphorylated on tyrosine residues
in a ligand-independent manner. E4ICD2 but not E4ICD1 is
phosphorylated on tyrosine residues. {ECO:0000269|PubMed:16251361,
ECO:0000269|PubMed:17120616, ECO:0000269|PubMed:17486069,
ECO:0000269|PubMed:18721752, ECO:0000269|PubMed:19098003,
ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9168115}.
-!- PTM: Ubiquitinated. During mitosis, the ERBB4 intracellular domain
is ubiquitinated by the APC/C complex and targeted to proteasomal
degradation. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are
ubiquitinated by WWP1. The ERBB4 intracellular domain (E4ICD1) is
ubiquitinated, and this involves NEDD4.
{ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19193720}.
-!- DISEASE: Amyotrophic lateral sclerosis 19 (ALS19) [MIM:615515]: A
neurodegenerative disorder affecting upper motor neurons in the
brain and lower motor neurons in the brain stem and spinal cord,
resulting in fatal paralysis. Sensory abnormalities are absent.
The pathologic hallmarks of the disease include pallor of the
corticospinal tract due to loss of motor neurons, presence of
ubiquitin-positive inclusions within surviving motor neurons, and
deposition of pathologic aggregates. The etiology of amyotrophic
lateral sclerosis is likely to be multifactorial, involving both
genetic and environmental factors. The disease is inherited in 5-
10% of the cases. {ECO:0000269|PubMed:24119685}. Note=The disease
is caused by mutations affecting the gene represented in this
entry.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
-!- CAUTION: Conflicting reports about the role of ERBB4 in mediating
apoptosis, differentiation, or tumor cell proliferation may be
explained by the opposite functions of the different isoforms and
their intracellular fragments, and by the formation of
heterodimers with other EGF receptor family members
(PubMed:18454307 and PubMed:21811097). Thus, heterodimer formation
of a kinase-dead ERBB4 mutant with ERBB2 is sufficient for the
activation of AKT1, MAPK1/ERK2 and MAPK3/ERK1 (PubMed:19098003).
{ECO:0000305|PubMed:19098003}.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; L07868; AAB59446.1; -; mRNA.
EMBL; BC112199; AAI12200.1; -; mRNA.
EMBL; BC143741; AAI43742.1; -; mRNA.
EMBL; BC143747; AAI43748.1; -; mRNA.
EMBL; BC143749; AAI43750.1; -; mRNA.
EMBL; AB209697; BAD92934.1; -; mRNA.
CCDS; CCDS2394.1; -. [Q15303-1]
CCDS; CCDS42811.1; -. [Q15303-3]
PIR; A47253; A47253.
RefSeq; NP_001036064.1; NM_001042599.1. [Q15303-3]
RefSeq; NP_005226.1; NM_005235.2. [Q15303-1]
RefSeq; XP_005246433.1; XM_005246376.2. [Q15303-2]
RefSeq; XP_005246434.1; XM_005246377.2. [Q15303-4]
UniGene; Hs.390729; -.
PDB; 2AHX; X-ray; 2.40 A; A/B=26-641.
PDB; 2L2T; NMR; -; A/B=642-685.
PDB; 2LCX; NMR; -; A/B=642-685.
PDB; 2R4B; X-ray; 2.40 A; A/B=690-999.
PDB; 3BBT; X-ray; 2.80 A; B/D=702-1029.
PDB; 3BBW; X-ray; 4.00 A; A/B=702-1029.
PDB; 3BCE; X-ray; 2.50 A; A/B/C=702-1029.
PDB; 3U2P; X-ray; 2.57 A; A=26-522.
PDB; 3U7U; X-ray; 3.03 A; A/B/C/D/E/F=26-640.
PDB; 3U9U; X-ray; 3.42 A; E/F=26-650.
PDBsum; 2AHX; -.
PDBsum; 2L2T; -.
PDBsum; 2LCX; -.
PDBsum; 2R4B; -.
PDBsum; 3BBT; -.
PDBsum; 3BBW; -.
PDBsum; 3BCE; -.
PDBsum; 3U2P; -.
PDBsum; 3U7U; -.
PDBsum; 3U9U; -.
ProteinModelPortal; Q15303; -.
SMR; Q15303; -.
BioGrid; 108378; 49.
DIP; DIP-29650N; -.
ELM; Q15303; -.
IntAct; Q15303; 26.
MINT; MINT-125091; -.
STRING; 9606.ENSP00000342235; -.
BindingDB; Q15303; -.
ChEMBL; CHEMBL3009; -.
DrugBank; DB08916; Afatinib.
GuidetoPHARMACOLOGY; 1799; -.
TCDB; 1.A.87.2.6; the mechanosensitive calcium channel (mca) family.
iPTMnet; Q15303; -.
PhosphoSitePlus; Q15303; -.
BioMuta; ERBB4; -.
DMDM; 3913590; -.
MaxQB; Q15303; -.
PaxDb; Q15303; -.
PeptideAtlas; Q15303; -.
PRIDE; Q15303; -.
DNASU; 2066; -.
Ensembl; ENST00000342788; ENSP00000342235; ENSG00000178568. [Q15303-1]
Ensembl; ENST00000436443; ENSP00000403204; ENSG00000178568. [Q15303-3]
GeneID; 2066; -.
KEGG; hsa:2066; -.
UCSC; uc002veg.2; human. [Q15303-1]
CTD; 2066; -.
DisGeNET; 2066; -.
GeneCards; ERBB4; -.
HGNC; HGNC:3432; ERBB4.
HPA; CAB000276; -.
HPA; CAB025522; -.
HPA; HPA012016; -.
MalaCards; ERBB4; -.
MIM; 600543; gene.
MIM; 615515; phenotype.
neXtProt; NX_Q15303; -.
OpenTargets; ENSG00000178568; -.
Orphanet; 803; Amyotrophic lateral sclerosis.
PharmGKB; PA27847; -.
eggNOG; KOG1025; Eukaryota.
eggNOG; ENOG410XNSR; LUCA.
GeneTree; ENSGT00760000118799; -.
HOGENOM; HOG000230982; -.
HOVERGEN; HBG000490; -.
InParanoid; Q15303; -.
KO; K05085; -.
OMA; RTRIDSN; -.
OrthoDB; EOG091G00EY; -.
PhylomeDB; Q15303; -.
TreeFam; TF106002; -.
BRENDA; 2.7.10.1; 2681.
Reactome; R-HSA-1227986; Signaling by ERBB2.
Reactome; R-HSA-1236394; Signaling by ERBB4.
Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling.
Reactome; R-HSA-1250342; PI3K events in ERBB4 signaling.
Reactome; R-HSA-1250347; SHC1 events in ERBB4 signaling.
Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
Reactome; R-HSA-1253288; Downregulation of ERBB4 signaling.
Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
Reactome; R-HSA-1963640; GRB2 events in ERBB2 signaling.
Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling.
Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
Reactome; R-HSA-6785631; ERBB2 Regulates Cell Motility.
Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
Reactome; R-HSA-8847993; ERBB2 Activates PTK6 Signaling.
Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling.
SignaLink; Q15303; -.
SIGNOR; Q15303; -.
ChiTaRS; ERBB4; human.
EvolutionaryTrace; Q15303; -.
GeneWiki; ERBB4; -.
GenomeRNAi; 2066; -.
PMAP-CutDB; Q15303; -.
PRO; PR:Q15303; -.
Proteomes; UP000005640; Chromosome 2.
Bgee; ENSG00000178568; -.
CleanEx; HS_ERBB4; -.
ExpressionAtlas; Q15303; baseline and differential.
Genevisible; Q15303; HS.
GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0043235; C:receptor complex; IDA:MGI.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:UniProtKB.
GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; TAS:Reactome.
GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome.
GO; GO:0004716; F:signal transducer, downstream of receptor, with protein tyrosine kinase activity; IEA:InterPro.
GO; GO:0044212; F:transcription regulatory region DNA binding; IMP:UniProtKB.
GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
GO; GO:0061026; P:cardiac muscle tissue regeneration; ISS:UniProtKB.
GO; GO:0045165; P:cell fate commitment; IEA:Ensembl.
GO; GO:0016477; P:cell migration; IDA:UniProtKB.
GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
GO; GO:0021551; P:central nervous system morphogenesis; ISS:UniProtKB.
GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
GO; GO:0038128; P:ERBB2 signaling pathway; TAS:Reactome.
GO; GO:0007507; P:heart development; ISS:UniProtKB.
GO; GO:0007595; P:lactation; IMP:UniProtKB.
GO; GO:0060749; P:mammary gland alveolus development; ISS:UniProtKB.
GO; GO:0060644; P:mammary gland epithelial cell differentiation; ISS:UniProtKB.
GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IMP:UniProtKB.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
GO; GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
GO; GO:1901185; P:negative regulation of ERBB signaling pathway; TAS:Reactome.
GO; GO:2001223; P:negative regulation of neuron migration; IEA:Ensembl.
GO; GO:0007399; P:nervous system development; ISS:UniProtKB.
GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
GO; GO:0021889; P:olfactory bulb interneuron differentiation; ISS:UniProtKB.
GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IEA:Ensembl.
GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:UniProtKB.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl.
GO; GO:0001934; P:positive regulation of protein phosphorylation; TAS:UniProtKB.
GO; GO:2000366; P:positive regulation of STAT protein import into nucleus; IMP:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
GO; GO:2000145; P:regulation of cell motility; TAS:Reactome.
GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; TAS:Reactome.
GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:UniProtKB.
Gene3D; 3.80.20.20; -; 3.
InterPro; IPR006211; Furin-like_Cys-rich_dom.
InterPro; IPR006212; Furin_repeat.
InterPro; IPR032778; GF_recep_IV.
InterPro; IPR009030; Growth_fac_rcpt_.
InterPro; IPR011009; Kinase-like_dom.
InterPro; IPR032675; L_dom-like.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR000494; Rcpt_L-dom.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008266; Tyr_kinase_AS.
InterPro; IPR020635; Tyr_kinase_cat_dom.
InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt.
Pfam; PF00757; Furin-like; 1.
Pfam; PF14843; GF_recep_IV; 1.
Pfam; PF07714; Pkinase_Tyr; 1.
Pfam; PF01030; Recep_L_domain; 2.
PIRSF; PIRSF000619; TyrPK_EGF-R; 1.
PRINTS; PR00109; TYRKINASE.
SMART; SM00261; FU; 5.
SMART; SM00219; TyrKc; 1.
SUPFAM; SSF52058; SSF52058; 2.
SUPFAM; SSF56112; SSF56112; 1.
SUPFAM; SSF57184; SSF57184; 2.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
1: Evidence at protein level;
3D-structure; Activator; Alternative splicing;
Amyotrophic lateral sclerosis; Apoptosis; ATP-binding; Cell membrane;
Complete proteome; Developmental protein; Disease mutation;
Disulfide bond; Glycoprotein; Kinase; Lactation; Membrane;
Mitochondrion; Neurodegeneration; Nucleotide-binding; Nucleus;
Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat;
Signal; Transcription; Transcription regulation; Transferase;
Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
Ubl conjugation.
SIGNAL 1 25 {ECO:0000255}.
CHAIN 26 1308 Receptor tyrosine-protein kinase erbB-4.
/FTId=PRO_0000016674.
CHAIN 676 1308 ERBB4 intracellular domain.
{ECO:0000250}.
/FTId=PRO_0000396797.
TOPO_DOM 26 651 Extracellular. {ECO:0000255}.
TRANSMEM 652 675 Helical. {ECO:0000255}.
TOPO_DOM 676 1308 Cytoplasmic. {ECO:0000255}.
DOMAIN 718 985 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 724 732 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 797 799 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 843 848 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOTIF 676 684 Nuclear localization signal.
MOTIF 1032 1035 PPxY motif 1.
MOTIF 1053 1056 PPxY motif 2.
MOTIF 1298 1301 PPxY motif 3.
MOTIF 1306 1308 PDZ-binding.
COMPBIAS 186 334 Cys-rich.
COMPBIAS 496 633 Cys-rich.
ACT_SITE 843 843 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10028}.
BINDING 751 751 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 875 875 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752}.
MOD_RES 1035 1035 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752}.
MOD_RES 1056 1056 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:17120616,
ECO:0000269|PubMed:18721752,
ECO:0000269|PubMed:8617750}.
MOD_RES 1150 1150 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752}.
MOD_RES 1162 1162 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752}.
MOD_RES 1188 1188 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752,
ECO:0000269|PubMed:8617750}.
MOD_RES 1202 1202 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752}.
MOD_RES 1242 1242 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752,
ECO:0000269|PubMed:8617750}.
MOD_RES 1258 1258 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752}.
MOD_RES 1284 1284 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:18721752}.
CARBOHYD 138 138 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 174 174 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 181 181 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 253 253 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 358 358 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 410 410 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 473 473 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 495 495 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 548 548 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 576 576 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16203964}.
CARBOHYD 620 620 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 29 56 {ECO:0000269|PubMed:16203964}.
DISULFID 156 186 {ECO:0000269|PubMed:16203964}.
DISULFID 189 197 {ECO:0000269|PubMed:16203964}.
DISULFID 193 205 {ECO:0000269|PubMed:16203964}.
DISULFID 213 221 {ECO:0000269|PubMed:16203964}.
DISULFID 217 229 {ECO:0000269|PubMed:16203964}.
DISULFID 230 238 {ECO:0000269|PubMed:16203964}.
DISULFID 234 246 {ECO:0000269|PubMed:16203964}.
DISULFID 249 258 {ECO:0000269|PubMed:16203964}.
DISULFID 262 289 {ECO:0000269|PubMed:16203964}.
DISULFID 293 304 {ECO:0000269|PubMed:16203964}.
DISULFID 308 323 {ECO:0000269|PubMed:16203964}.
DISULFID 326 330 {ECO:0000269|PubMed:16203964}.
DISULFID 503 512 {ECO:0000269|PubMed:16203964}.
DISULFID 507 520 {ECO:0000269|PubMed:16203964}.
DISULFID 523 532 {ECO:0000269|PubMed:16203964}.
DISULFID 536 552 {ECO:0000269|PubMed:16203964}.
DISULFID 555 569 {ECO:0000269|PubMed:16203964}.
DISULFID 559 577 {ECO:0000269|PubMed:16203964}.
DISULFID 580 589 {ECO:0000269|PubMed:16203964}.
DISULFID 593 614 {ECO:0000269|PubMed:16203964}.
DISULFID 617 625 {ECO:0000269|PubMed:16203964}.
DISULFID 621 633 {ECO:0000269|PubMed:16203964}.
VAR_SEQ 626 648 NGPTSHDCIYYPWTGHSTLPQHA -> IGSSIEDCIGLMD
(in isoform JM-B CYT-1 and isoform JM-B
CYT-2). {ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:9334263}.
/FTId=VSP_002895.
VAR_SEQ 1046 1061 Missing (in isoform JM-A CYT-2 and
isoform JM-B CYT-2).
{ECO:0000303|PubMed:15489334,
ECO:0000303|Ref.4}.
/FTId=VSP_022148.
VARIANT 140 140 T -> I (in a colorectal adenocarcinoma
sample; somatic mutation).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_042113.
VARIANT 303 303 S -> Y (in a lung squamous cell carcinoma
sample; somatic mutation).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_042114.
VARIANT 927 927 R -> Q (in ALS19; reduces
autophosphorylation upon NRG1
stimulation; dbSNP:rs397514262).
{ECO:0000269|PubMed:24119685}.
/FTId=VAR_070810.
VARIANT 1275 1275 R -> W (in ALS19; reduces
autophosphorylation upon NRG1
stimulation; dbSNP:rs397514263).
{ECO:0000269|PubMed:24119685}.
/FTId=VAR_070811.
MUTAGEN 646 646 Q->C: Constitutively activated kinase.
{ECO:0000269|PubMed:17120616}.
MUTAGEN 675 675 V->A: Abolishes proteolytic processing
and nuclear localization.
{ECO:0000269|PubMed:15746097,
ECO:0000269|PubMed:17638867}.
MUTAGEN 681 684 KKKR->EIMG: Abolishes nuclear
localization of the ERBB4 intracellular
domain. {ECO:0000269|PubMed:15534001}.
MUTAGEN 710 710 L->N: Strongly reduced
autophosphorylation.
{ECO:0000269|PubMed:18287036}.
MUTAGEN 721 721 V->I: No effect on kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 751 751 K->R: Abolishes kinase activity.
Abolishes phosphorylation, proteolytic
processing and nuclear localization.
{ECO:0000269|PubMed:11390655,
ECO:0000269|PubMed:17486069,
ECO:0000269|PubMed:17638867}.
MUTAGEN 766 766 M->R: Strongly reduced
autophosphorylation.
{ECO:0000269|PubMed:18287036}.
MUTAGEN 773 773 A->S: No effect on kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 782 782 R->Q: No effect on kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 810 810 E->K: No effect on kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 843 843 D->N: Loss of kinase activity.
{ECO:0000269|PubMed:16978839}.
MUTAGEN 854 854 P->Q: No effect on kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 861 861 D->Y: Loss of kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 864 864 L->R: Strongly reduced
autophosphorylation.
{ECO:0000269|PubMed:18287036}.
MUTAGEN 872 872 E->K: No effect on kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 926 926 T->M: No effect on kinase activity.
{ECO:0000269|PubMed:19098003}.
MUTAGEN 947 947 I->R: Constitutively autophosphorylated.
{ECO:0000269|PubMed:18287036}.
MUTAGEN 992 992 R->A: Abolishes APC/C-mediated
degradation; when associated with A-995
and A-1000.
{ECO:0000269|PubMed:17638867}.
MUTAGEN 995 995 L->A: Abolishes APC/C-mediated
degradation; when associated with A-992
and A-1000.
{ECO:0000269|PubMed:17638867}.
MUTAGEN 1000 1000 D->A: Abolishes APC/C-mediated
degradation; when associated with A-992
and A-995. {ECO:0000269|PubMed:17638867}.
MUTAGEN 1035 1035 Y->A: No effect on interaction with WWOX.
Abolishes interaction with WWOX; when
associated with A-1301.
{ECO:0000269|PubMed:16061658}.
MUTAGEN 1056 1056 Y->A: Abolishes interaction with NEDD4
and impairs ubiquitination. Promotes
nuclear translocation of ERBB4
intracellular domain E4ICD1.
{ECO:0000269|PubMed:19561640}.
MUTAGEN 1056 1056 Y->F: Abolishes interaction with WWP1;
when associated with F-1301.
{ECO:0000269|PubMed:19561640}.
MUTAGEN 1301 1301 Y->A: Abolishes interaction with NEDD4
and impairs ubiquitination.
{ECO:0000269|PubMed:12807903,
ECO:0000269|PubMed:16061658,
ECO:0000269|PubMed:19561640}.
MUTAGEN 1301 1301 Y->A: No effect on interaction with WWOX.
Abolishes interaction with WWOX; when
associated with A-1035. Loss of
interaction with YAP1 and stimulation of
transcription.
{ECO:0000269|PubMed:12807903,
ECO:0000269|PubMed:16061658,
ECO:0000269|PubMed:19561640}.
MUTAGEN 1301 1301 Y->F: Abolishes interaction with WWP1;
when associated with F-1056.
{ECO:0000269|PubMed:12807903,
ECO:0000269|PubMed:16061658,
ECO:0000269|PubMed:19561640}.
STRAND 28 30 {ECO:0000244|PDB:2AHX}.
STRAND 38 41 {ECO:0000244|PDB:3U7U}.
HELIX 42 53 {ECO:0000244|PDB:2AHX}.
STRAND 57 61 {ECO:0000244|PDB:2AHX}.
STRAND 63 67 {ECO:0000244|PDB:2AHX}.
HELIX 75 79 {ECO:0000244|PDB:2AHX}.
STRAND 82 85 {ECO:0000244|PDB:2AHX}.
STRAND 87 91 {ECO:0000244|PDB:2AHX}.
STRAND 95 98 {ECO:0000244|PDB:2AHX}.
TURN 112 114 {ECO:0000244|PDB:2AHX}.
STRAND 115 120 {ECO:0000244|PDB:2AHX}.
STRAND 125 128 {ECO:0000244|PDB:3U2P}.
STRAND 133 135 {ECO:0000244|PDB:2AHX}.
STRAND 144 150 {ECO:0000244|PDB:2AHX}.
HELIX 158 160 {ECO:0000244|PDB:2AHX}.
HELIX 163 165 {ECO:0000244|PDB:2AHX}.
HELIX 173 175 {ECO:0000244|PDB:2AHX}.
STRAND 176 178 {ECO:0000244|PDB:2AHX}.
TURN 191 193 {ECO:0000244|PDB:2AHX}.
STRAND 197 201 {ECO:0000244|PDB:2AHX}.
HELIX 202 204 {ECO:0000244|PDB:2AHX}.
STRAND 221 225 {ECO:0000244|PDB:2AHX}.
HELIX 226 228 {ECO:0000244|PDB:2AHX}.
STRAND 234 242 {ECO:0000244|PDB:2AHX}.
STRAND 245 254 {ECO:0000244|PDB:2AHX}.
STRAND 257 261 {ECO:0000244|PDB:2AHX}.
STRAND 265 269 {ECO:0000244|PDB:2AHX}.
TURN 270 273 {ECO:0000244|PDB:2AHX}.
STRAND 274 277 {ECO:0000244|PDB:2AHX}.
STRAND 283 285 {ECO:0000244|PDB:2AHX}.
STRAND 288 292 {ECO:0000244|PDB:2AHX}.
STRAND 298 300 {ECO:0000244|PDB:2AHX}.
STRAND 303 307 {ECO:0000244|PDB:2AHX}.
STRAND 312 317 {ECO:0000244|PDB:2AHX}.
STRAND 320 325 {ECO:0000244|PDB:2AHX}.
STRAND 327 329 {ECO:0000244|PDB:3U2P}.
STRAND 333 335 {ECO:0000244|PDB:2AHX}.
HELIX 340 342 {ECO:0000244|PDB:2AHX}.
TURN 350 352 {ECO:0000244|PDB:2AHX}.
HELIX 353 356 {ECO:0000244|PDB:2AHX}.
STRAND 360 364 {ECO:0000244|PDB:2AHX}.
STRAND 366 368 {ECO:0000244|PDB:2AHX}.
HELIX 370 374 {ECO:0000244|PDB:2AHX}.
HELIX 377 379 {ECO:0000244|PDB:2AHX}.
HELIX 386 394 {ECO:0000244|PDB:2AHX}.
STRAND 397 400 {ECO:0000244|PDB:2AHX}.
STRAND 402 405 {ECO:0000244|PDB:2AHX}.
HELIX 415 417 {ECO:0000244|PDB:2AHX}.
STRAND 432 438 {ECO:0000244|PDB:2AHX}.
STRAND 455 461 {ECO:0000244|PDB:2AHX}.
HELIX 469 471 {ECO:0000244|PDB:2AHX}.
HELIX 474 476 {ECO:0000244|PDB:2AHX}.
STRAND 479 482 {ECO:0000244|PDB:2AHX}.
STRAND 485 487 {ECO:0000244|PDB:2AHX}.
STRAND 489 491 {ECO:0000244|PDB:2AHX}.
HELIX 493 497 {ECO:0000244|PDB:2AHX}.
TURN 498 500 {ECO:0000244|PDB:2AHX}.
STRAND 512 516 {ECO:0000244|PDB:2AHX}.
STRAND 519 528 {ECO:0000244|PDB:2AHX}.
STRAND 531 534 {ECO:0000244|PDB:2AHX}.
STRAND 537 543 {ECO:0000244|PDB:2AHX}.
STRAND 545 548 {ECO:0000244|PDB:2AHX}.
STRAND 551 554 {ECO:0000244|PDB:2AHX}.
STRAND 568 573 {ECO:0000244|PDB:2AHX}.
STRAND 576 585 {ECO:0000244|PDB:2AHX}.
STRAND 588 592 {ECO:0000244|PDB:2AHX}.
STRAND 595 608 {ECO:0000244|PDB:2AHX}.
STRAND 612 616 {ECO:0000244|PDB:2AHX}.
STRAND 625 629 {ECO:0000244|PDB:2AHX}.
HELIX 651 676 {ECO:0000244|PDB:2L2T}.
HELIX 715 717 {ECO:0000244|PDB:2R4B}.
STRAND 718 729 {ECO:0000244|PDB:2R4B}.
STRAND 731 737 {ECO:0000244|PDB:2R4B}.
STRAND 740 743 {ECO:0000244|PDB:3BBT}.
STRAND 746 752 {ECO:0000244|PDB:2R4B}.
HELIX 762 773 {ECO:0000244|PDB:2R4B}.
STRAND 778 780 {ECO:0000244|PDB:3BBT}.
STRAND 783 787 {ECO:0000244|PDB:2R4B}.
STRAND 789 791 {ECO:0000244|PDB:2R4B}.
STRAND 793 797 {ECO:0000244|PDB:2R4B}.
HELIX 804 810 {ECO:0000244|PDB:2R4B}.
HELIX 812 814 {ECO:0000244|PDB:2R4B}.
HELIX 817 836 {ECO:0000244|PDB:2R4B}.
HELIX 846 848 {ECO:0000244|PDB:2R4B}.
STRAND 849 853 {ECO:0000244|PDB:2R4B}.
STRAND 856 859 {ECO:0000244|PDB:2R4B}.
HELIX 864 869 {ECO:0000244|PDB:2R4B}.
HELIX 884 886 {ECO:0000244|PDB:2R4B}.
HELIX 889 893 {ECO:0000244|PDB:2R4B}.
HELIX 899 914 {ECO:0000244|PDB:2R4B}.
TURN 920 923 {ECO:0000244|PDB:2R4B}.
TURN 926 928 {ECO:0000244|PDB:2R4B}.
HELIX 929 934 {ECO:0000244|PDB:2R4B}.
HELIX 947 955 {ECO:0000244|PDB:2R4B}.
HELIX 961 963 {ECO:0000244|PDB:2R4B}.
HELIX 967 977 {ECO:0000244|PDB:2R4B}.
HELIX 981 983 {ECO:0000244|PDB:2R4B}.
SEQUENCE 1308 AA; 146808 MW; 5E4AE80985D88761 CRC64;
MKPATGLWVW VSLLVAAGTV QPSDSQSVCA GTENKLSSLS DLEQQYRALR KYYENCEVVM
GNLEITSIEH NRDLSFLRSV REVTGYVLVA LNQFRYLPLE NLRIIRGTKL YEDRYALAIF
LNYRKDGNFG LQELGLKNLT EILNGGVYVD QNKFLCYADT IHWQDIVRNP WPSNLTLVST
NGSSGCGRCH KSCTGRCWGP TENHCQTLTR TVCAEQCDGR CYGPYVSDCC HRECAGGCSG
PKDTDCFACM NFNDSGACVT QCPQTFVYNP TTFQLEHNFN AKYTYGAFCV KKCPHNFVVD
SSSCVRACPS SKMEVEENGI KMCKPCTDIC PKACDGIGTG SLMSAQTVDS SNIDKFINCT
KINGNLIFLV TGIHGDPYNA IEAIDPEKLN VFRTVREITG FLNIQSWPPN MTDFSVFSNL
VTIGGRVLYS GLSLLILKQQ GITSLQFQSL KEISAGNIYI TDNSNLCYYH TINWTTLFST
INQRIVIRDN RKAENCTAEG MVCNHLCSSD GCWGPGPDQC LSCRRFSRGR ICIESCNLYD
GEFREFENGS ICVECDPQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDGLQGA
NSFIFKYADP DRECHPCHPN CTQGCNGPTS HDCIYYPWTG HSTLPQHART PLIAAGVIGG
LFILVIVGLT FAVYVRRKSI KKKRALRRFL ETELVEPLTP SGTAPNQAQL RILKETELKR
VKVLGSGAFG TVYKGIWVPE GETVKIPVAI KILNETTGPK ANVEFMDEAL IMASMDHPHL
VRLLGVCLSP TIQLVTQLMP HGCLLEYVHE HKDNIGSQLL LNWCVQIAKG MMYLEERRLV
HRDLAARNVL VKSPNHVKIT DFGLARLLEG DEKEYNADGG KMPIKWMALE CIHYRKFTHQ
SDVWSYGVTI WELMTFGGKP YDGIPTREIP DLLEKGERLP QPPICTIDVY MVMVKCWMID
ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND SKFFQNLLDE EDLEDMMDAE
EYLVPQAFNI PPPIYTSRAR IDSNRSEIGH SPPPAYTPMS GNQFVYRDGG FAAEQGVSVP
YRAPTSTIPE APVAQGATAE IFDDSCCNGT LRKPVAPHVQ EDSSTQRYSA DPTVFAPERS
PRGELDEEGY MTPMRDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHN ASNGPPKAED
EYVNEPLYLN TFANTLGKAE YLKNNILSMP EKAKKAFDNP DYWNHSLPPR STLQHPDYLQ
EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTVLPPPP YRHRNTVV


Related products :

Catalog number Product name Quantity
EIAAB13165 ERBB4,HER4,Homo sapiens,Human,p180erbB4,Proto-oncogene-like protein c-ErbB-4,Receptor tyrosine-protein kinase erbB-4,Tyrosine kinase-type cell surface receptor HER4
15-288-22631 Receptor tyrosine-protein kinase erbB-2 - EC 2.7.10.1; p185erbB2; C-erbB-2; NEU proto-oncogene; Tyrosine kinase-type cell surface receptor HER2; MLN 19 Polyclonal 0.1 mg
15-288-22631 Receptor tyrosine-protein kinase erbB-2 - EC 2.7.10.1; p185erbB2; C-erbB-2; NEU proto-oncogene; Tyrosine kinase-type cell surface receptor HER2; MLN 19 Polyclonal 0.05 mg
EIAAB13162 ERBB3,HER3,Homo sapiens,Human,Proto-oncogene-like protein c-ErbB-3,Receptor tyrosine-protein kinase erbB-3,Tyrosine kinase-type cell surface receptor HER3
18-272-196265 ErbB 4 - Rabbit polyclonal to ErbB 4; EC 2.7.10.1; p180erbB4; Tyrosine kinase-type cell surface receptor HER4 Polyclonal 0.5 ml
EIAAB13166 Erbb4,Proto-oncogene-like protein c-ErbB-4,Rat,Rattus norvegicus,Receptor tyrosine-protein kinase erbB-4,Tyro-2
EIAAB13167 Erbb4,Mer4,Mouse,Mus musculus,Proto-oncogene-like protein c-ErbB-4,Receptor tyrosine-protein kinase erbB-4
18-272-196267 ErbB 4 prediluted - Rabbit polyclonal to ErbB 4 prediluted; EC 2.7.10.1; p180erbB4; Tyrosine kinase-type cell surface receptor HER4 Polyclonal 7 ml
20-272-191691 ErbB 4. prediluted - Mouse monoclonal [SPM338] to ErbB 4. prediluted; EC 2.7.10.1; p180erbB4; Tyrosine kinase-type cell surface receptor HER4 Monoclonal 7 ml
E0978h ELISA ERBB2,HER2,Homo sapiens,Human,Metastatic lymph node gene 19 protein,MLN 19,MLN19,NEU,NGL,p185erbB2,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Receptor tyrosine-protein kinase erbB-2,Tyrosine kin 96T
U0978h CLIA ERBB2,HER2,Homo sapiens,Human,Metastatic lymph node gene 19 protein,MLN 19,MLN19,NEU,NGL,p185erbB2,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Receptor tyrosine-protein kinase erbB-2,Tyrosine kina 96T
E0978r ELISA Epidermal growth factor receptor-related protein,Erbb2,Neu,p185erbB2,p185neu,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Rat,Rattus norvegicus,Receptor tyrosine-protein kinase erbB-2 96T
E0978r ELISA kit Epidermal growth factor receptor-related protein,Erbb2,Neu,p185erbB2,p185neu,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Rat,Rattus norvegicus,Receptor tyrosine-protein kinase erbB-2 96T
U0978r CLIA Epidermal growth factor receptor-related protein,Erbb2,Neu,p185erbB2,p185neu,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Rat,Rattus norvegicus,Receptor tyrosine-protein kinase erbB-2 96T
E0978m ELISA kit Erbb2,Kiaa3023,Mouse,Mus musculus,Neu,p185erbB2,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Receptor tyrosine-protein kinase erbB-2 96T
U0978m CLIA Erbb2,Kiaa3023,Mouse,Mus musculus,Neu,p185erbB2,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Receptor tyrosine-protein kinase erbB-2 96T
E0978m ELISA Erbb2,Kiaa3023,Mouse,Mus musculus,Neu,p185erbB2,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Receptor tyrosine-protein kinase erbB-2 96T
E0978h ELISA kit ERBB2,HER2,Homo sapiens,Human,Metastatic lymph node gene 19 protein,MLN 19,MLN19,NEU,NGL,p185erbB2,Proto-oncogene c-ErbB-2,Proto-oncogene Neu,Receptor tyrosine-protein kinase erbB-2,Tyrosin 96T
EIAAB13163 Erbb3,Glial growth factor receptor,Mouse,Mus musculus,Proto-oncogene-like protein c-ErbB-3,Receptor tyrosine-protein kinase erbB-3
U0757h CLIA EGFR,Epidermal growth factor receptor,ERBB1,Homo sapiens,Human,Proto-oncogene c-ErbB-1,Receptor tyrosine-protein kinase erbB-1 96T
E0757h ELISA kit EGFR,Epidermal growth factor receptor,ERBB1,Homo sapiens,Human,Proto-oncogene c-ErbB-1,Receptor tyrosine-protein kinase erbB-1 96T
E0757h ELISA EGFR,Epidermal growth factor receptor,ERBB1,Homo sapiens,Human,Proto-oncogene c-ErbB-1,Receptor tyrosine-protein kinase erbB-1 96T
EIAAB13164 Erbb3,Proto-oncogene-like protein c-ErbB-3,Rat,Rattus norvegicus,Receptor tyrosine-protein kinase erbB-3
18-785-210195 HER2 (Ab-877) - EC 2.7.10.1; p185erbB2; C-erbB-2; NEU proto-oncogene; Tyrosine kinase-type cell surface receptor HER2; MLN 19; CD340 antigen Polyclonal 0.05 mg
18-785-210195 HER2 (Ab-877) - EC 2.7.10.1; p185erbB2; C-erbB-2; NEU proto-oncogene; Tyrosine kinase-type cell surface receptor HER2; MLN 19; CD340 antigen Polyclonal 0.1 mg


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur