ERBB3_HUMAN
ID ERBB3_HUMAN Reviewed; 1342 AA.
AC P21860; A8K6L6; B4DIK7; B4DV32; E9PDT8; Q9BUD7;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=Receptor tyrosine-protein kinase erbB-3;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene-like protein c-ErbB-3;
DE AltName: Full=Tyrosine kinase-type cell surface receptor HER3;
DE Flags: Precursor;
GN Name=ERBB3; Synonyms=HER3;
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=2687875; DOI=10.1073/pnas.86.23.9193;
RA Kraus M.H., Issing W., Miki T., Popescu N.C., Aaronson S.A.;
RT "Isolation and characterization of ERBB3, a third member of the
RT ERBB/epidermal growth factor receptor family: evidence for overexpression
RT in a subset of human mammary tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:9193-9197(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2164210; DOI=10.1073/pnas.87.13.4905;
RA Plowman G.D., Whitney G.S., Neubauer M.G., Green J.M., McDonald V.L.,
RA Todaro G.J., Shoyab M.;
RT "Molecular cloning and expression of an additional epidermal growth factor
RT receptor-related gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:4905-4909(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=7685162; DOI=10.1006/bbrc.1993.1542;
RA Katoh M., Yazaki Y., Sugimura T., Terada M.;
RT "c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine
RT kinase.";
RL Biochem. Biophys. Res. Commun. 192:1189-1197(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 4 AND 5).
RC TISSUE=Hippocampus, Placenta, and Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Skin;
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 [8]
RP INTERACTION WITH GRB7.
RX PubMed=9516479; DOI=10.1074/jbc.273.13.7717;
RA Fiddes R.J., Campbell D.H., Janes P.W., Sivertsen S.P., Sasaki H.,
RA Wallasch C., Daly R.J.;
RT "Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals
RT a novel target selectivity for erbB3.";
RL J. Biol. Chem. 273:7717-7724(1998).
RN [9]
RP INTERACTION WITH PA2G4.
RX PubMed=11325528; DOI=10.1016/s0303-7207(01)00387-2;
RA Lessor T.J., Hamburger A.W.;
RT "Regulation of the ErbB3 binding protein Ebp1 by protein kinase C.";
RL Mol. Cell. Endocrinol. 175:185-191(2001).
RN [10]
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 [11]
RP INTERACTION WITH CSPG5, AND FUNCTION.
RX PubMed=15358134; DOI=10.1016/j.bbrc.2004.07.066;
RA Kinugasa Y., Ishiguro H., Tokita Y., Oohira A., Ohmoto H., Higashiyama S.;
RT "Neuroglycan C, a novel member of the neuregulin family.";
RL Biochem. Biophys. Res. Commun. 321:1045-1049(2004).
RN [12]
RP INTERACTION WITH PA2G4.
RX PubMed=16832058; DOI=10.1073/pnas.0602923103;
RA Liu Z., Ahn J.Y., Liu X., Ye K.;
RT "Ebp1 isoforms distinctively regulate cell survival and differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10917-10922(2006).
RN [13]
RP INVOLVEMENT IN LCCS2.
RX PubMed=17701904; DOI=10.1086/520770;
RA Narkis G., Ofir R., Manor E., Landau D., Elbedour K., Birk O.S.;
RT "Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a
RT mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-
RT kinase/Akt pathway.";
RL Am. J. Hum. Genet. 81:589-595(2007).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP FUNCTION, BINDING TO NRG1, IDENTIFICATION IN A COMPLEX WITH NRG1 AND
RP INTEGRINS, AND PHOSPHORYLATION.
RX PubMed=20682778; DOI=10.1074/jbc.m110.113878;
RA Ieguchi K., Fujita M., Ma Z., Davari P., Taniguchi Y., Sekiguchi K.,
RA Wang B., Takada Y.K., Takada Y.;
RT "Direct binding of the EGF-like domain of neuregulin-1 to integrins
RT ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB
RT signaling.";
RL J. Biol. Chem. 285:31388-31398(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686, AND IDENTIFICATION BY
RP 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686 AND SER-982, 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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 20-640, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-250; ASN-353; ASN-408; ASN-414; ASN-437; ASN-469;
RP ASN-522 AND ASN-566.
RX PubMed=12154198; DOI=10.1126/science.1074611;
RA Cho H.S., Leahy D.J.;
RT "Structure of the extracellular region of HER3 reveals an interdomain
RT tether.";
RL Science 297:1330-1333(2002).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 698-1019 IN COMPLEX WITH AMP-PNP,
RP AND SUBUNIT.
RX PubMed=20007378; DOI=10.1073/pnas.0912101106;
RA Jura N., Shan Y., Cao X., Shaw D.E., Kuriyan J.;
RT "Structural analysis of the catalytically inactive kinase domain of the
RT human EGF receptor 3.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:21608-21613(2009).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 684-1020 IN COMPLEX WITH AMP-PNP,
RP CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-742 AND TYR-868,
RP AUTOPHOSPHORYLATION, AND SUBUNIT.
RX PubMed=20351256; DOI=10.1073/pnas.1002753107;
RA Shi F., Telesco S.E., Liu Y., Radhakrishnan R., Lemmon M.A.;
RT "ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze
RT autophosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:7692-7697(2010).
RN [21]
RP STRUCTURE BY NMR OF 640-670, AND SUBUNIT.
RX PubMed=21575594; DOI=10.1016/j.bbamem.2011.04.017;
RA Mineev K.S., Khabibullina N.F., Lyukmanova E.N., Dolgikh D.A.,
RA Kirpichnikov M.P., Arseniev A.S.;
RT "Spatial structure and dimer-monomer equilibrium of the ErbB3 transmembrane
RT domain in DPC micelles.";
RL Biochim. Biophys. Acta 1808:2081-2088(2011).
RN [22]
RP VARIANTS [LARGE SCALE ANALYSIS] TYR-20; LEU-30; MET-104; ILE-204; TRP-683;
RP LEU-717; THR-744; ARG-998; CYS-1119; HIS-1127; ILE-1177 AND LYS-1254.
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 [23]
RP VARIANT FERLK THR-1337, CHARACTERIZATION OF VARIANT FERLK THR-1337,
RP INVOLVEMENT IN FERLK, AND FUNCTION.
RX PubMed=27416908; DOI=10.1038/leu.2016.173;
RA Braunstein E.M., Li R., Sobreira N., Marosy B., Hetrick K., Doheny K.,
RA Gocke C.D., Valle D., Brodsky R.A., Cheng L.;
RT "A germline ERBB3 variant is a candidate for predisposition to erythroid
RT MDS/erythroleukemia.";
RL Leukemia 30:2242-2245(2016).
RN [24]
RP INVOLVEMENT IN VSCN1, VARIANTS VSCN1 PRO-787; SER-873; MET-899 AND ARG-932,
RP CHARACTERIZATION OF VARIANTS VSCN1 PRO-787; SER-873; MET-899 AND ARG-932,
RP 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: Tyrosine-protein kinase that plays an essential role as cell
CC surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is
CC activated by it; ligand-binding increases phosphorylation on tyrosine
CC residues and promotes its association with the p85 subunit of
CC phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated
CC by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell
CC differentiation (PubMed:27416908). {ECO:0000269|PubMed:15358134,
CC ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:27416908}.
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:0000269|PubMed:20351256};
CC -!- SUBUNIT: Monomer and homodimer. Heterodimer with each of the other ERBB
CC receptors (Potential). Interacts with CSPG5 (PubMed:15358134).
CC Interacts with GRB7 (PubMed:9516479). Interacts with MUC1
CC (PubMed:12939402). Interacts with MYOC (By similarity). Interacts with
CC isoform 2 of PA2G4 (PubMed:11325528, PubMed:16832058). Found in a
CC ternary complex with NRG1 and ITGAV:ITGB3 or ITGA6:ITGB4
CC (PubMed:20682778). {ECO:0000250|UniProtKB:Q61526,
CC ECO:0000269|PubMed:11325528, ECO:0000269|PubMed:12939402,
CC ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:16832058,
CC ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:9516479, ECO:0000305}.
CC -!- INTERACTION:
CC P21860; P42684: ABL2; NbExp=10; IntAct=EBI-720706, EBI-1102694;
CC P21860; P46108: CRK; NbExp=2; IntAct=EBI-720706, EBI-886;
CC P21860; P46109: CRKL; NbExp=3; IntAct=EBI-720706, EBI-910;
CC P21860; P00533: EGFR; NbExp=13; IntAct=EBI-720706, EBI-297353;
CC P21860; P04626: ERBB2; NbExp=29; IntAct=EBI-720706, EBI-641062;
CC P21860; P21860: ERBB3; NbExp=2; IntAct=EBI-720706, EBI-720706;
CC P21860; Q15303: ERBB4; NbExp=4; IntAct=EBI-720706, EBI-80371;
CC P21860; P62993: GRB2; NbExp=3; IntAct=EBI-720706, EBI-401755;
CC P21860; Q14451: GRB7; NbExp=7; IntAct=EBI-720706, EBI-970191;
CC P21860; P25098: GRK2; NbExp=3; IntAct=EBI-720706, EBI-3904795;
CC P21860; P08631: HCK; NbExp=2; IntAct=EBI-720706, EBI-346340;
CC P21860; P08238: HSP90AB1; NbExp=3; IntAct=EBI-720706, EBI-352572;
CC P21860; Q96JA1: LRIG1; NbExp=2; IntAct=EBI-720706, EBI-2865191;
CC P21860; O43639: NCK2; NbExp=2; IntAct=EBI-720706, EBI-713635;
CC P21860; Q02297-6: NRG1; NbExp=2; IntAct=EBI-720706, EBI-15651799;
CC P21860; Q02297-7: NRG1; NbExp=3; IntAct=EBI-720706, EBI-2460927;
CC P21860; P42336: PIK3CA; NbExp=3; IntAct=EBI-720706, EBI-2116585;
CC P21860; P27986: PIK3R1; NbExp=41; IntAct=EBI-720706, EBI-79464;
CC P21860; O00459: PIK3R2; NbExp=16; IntAct=EBI-720706, EBI-346930;
CC P21860; Q92569: PIK3R3; NbExp=22; IntAct=EBI-720706, EBI-79893;
CC P21860; P19174: PLCG1; NbExp=4; IntAct=EBI-720706, EBI-79387;
CC P21860; P20936: RASA1; NbExp=6; IntAct=EBI-720706, EBI-1026476;
CC P21860; Q13671: RIN1; NbExp=2; IntAct=EBI-720706, EBI-366017;
CC P21860; P26447: S100A4; NbExp=4; IntAct=EBI-720706, EBI-717058;
CC P21860; P04271: S100B; NbExp=3; IntAct=EBI-720706, EBI-458391;
CC P21860; Q9UQQ2: SH2B3; NbExp=2; IntAct=EBI-720706, EBI-7879749;
CC P21860; P29353: SHC1; NbExp=5; IntAct=EBI-720706, EBI-78835;
CC P21860; Q92529: SHC3; NbExp=2; IntAct=EBI-720706, EBI-79084;
CC P21860; P12931: SRC; NbExp=2; IntAct=EBI-720706, EBI-621482;
CC P21860; P43405: SYK; NbExp=6; IntAct=EBI-720706, EBI-78302;
CC P21860; Q63HR2: TNS2; NbExp=3; IntAct=EBI-720706, EBI-949753;
CC P21860; Q68CZ2: TNS3; NbExp=2; IntAct=EBI-720706, EBI-1220488;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:33497358}; Single-pass type I membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=long form;
CC IsoId=P21860-1; Sequence=Displayed;
CC Name=2; Synonyms=short form;
CC IsoId=P21860-2; Sequence=VSP_002893, VSP_002894;
CC Name=3;
CC IsoId=P21860-3; Sequence=VSP_041663, VSP_041664;
CC Name=4;
CC IsoId=P21860-4; Sequence=VSP_041662;
CC Name=5;
CC IsoId=P21860-5; Sequence=VSP_041661;
CC -!- TISSUE SPECIFICITY: Epithelial tissues and brain.
CC -!- DEVELOPMENTAL STAGE: Overexpressed in a subset of human mammary tumors.
CC -!- DOMAIN: The cytoplasmic part of the receptor may interact with the SH2
CC or SH3 domains of many signal-transducing proteins.
CC -!- PTM: Autophosphorylated (PubMed:20351256). Ligand-binding increases
CC phosphorylation on tyrosine residues and promotes its association with
CC the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778).
CC {ECO:0000269|PubMed:20351256, ECO:0000269|PubMed:20682778,
CC ECO:0000269|PubMed:33497358}.
CC -!- DISEASE: Lethal congenital contracture syndrome 2 (LCCS2) [MIM:607598]:
CC A form of lethal congenital contracture syndrome, an autosomal
CC recessive disorder characterized by degeneration of anterior horn
CC neurons, extreme skeletal muscle atrophy, and congenital non-
CC progressive joint contractures (arthrogryposis). The contractures can
CC involve the upper or lower limbs and/or the vertebral column, leading
CC to various degrees of flexion or extension limitations evident at
CC birth. LCCS2 patients manifest craniofacial/ocular findings, lack of
CC hydrops, multiple pterygia, and fractures, as well as a normal duration
CC of pregnancy and a unique feature of a markedly distended urinary
CC bladder (neurogenic bladder defect). The phenotype suggests a spinal
CC cord neuropathic etiology. {ECO:0000269|PubMed:17701904}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Erythroleukemia, familial (FERLK) [MIM:133180]: An autosomal
CC dominant myeloproliferative disorder characterized by neoplastic
CC proliferation of erythroblastic and myeloblastic elements with atypical
CC erythroblasts and myeloblasts in the peripheral blood. Disease
CC penetrance is incomplete. {ECO:0000269|PubMed:27416908}. Note=Disease
CC susceptibility may be associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Visceral neuropathy, familial, 1, autosomal recessive (VSCN1)
CC [MIM:243180]: An autosomal recessive disorder characterized by
CC intestinal dysmotility due to aganglionosis (Hirschsprung disease),
CC hypoganglionosis, and/or chronic intestinal pseudoobstruction.
CC Additional variable features are progressive peripheral neuropathy,
CC arthrogryposis, hypoplasia or aplasia of the olfactory bulb and of the
CC external auditory canals, microtia or anotia, and facial dysmorphism.
CC Some patients present structural cardiac anomalies and arthrogryposis
CC with multiple pterygia. {ECO:0000269|PubMed:33497358}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
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/ERBB3ID40479ch12q13.html";
CC ---------------------------------------------------------------------------
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DR EMBL; M29366; AAA35790.1; -; mRNA.
DR EMBL; M34309; AAA35979.1; -; mRNA.
DR EMBL; S61953; AAB26935.1; -; mRNA.
DR EMBL; BT007226; AAP35890.1; -; mRNA.
DR EMBL; AK291681; BAF84370.1; -; mRNA.
DR EMBL; AK295650; BAG58519.1; -; mRNA.
DR EMBL; AK300909; BAG62544.1; -; mRNA.
DR EMBL; AC034102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002706; AAH02706.1; -; mRNA.
DR EMBL; BC082992; AAH82992.1; -; mRNA.
DR CCDS; CCDS31833.1; -. [P21860-1]
DR CCDS; CCDS44918.1; -. [P21860-2]
DR PIR; A36223; A36223.
DR PIR; JH0803; JH0803.
DR RefSeq; NP_001005915.1; NM_001005915.1. [P21860-2]
DR RefSeq; NP_001973.2; NM_001982.3. [P21860-1]
DR PDB; 1M6B; X-ray; 2.60 A; A/B=20-640.
DR PDB; 2L9U; NMR; -; A/B=639-670.
DR PDB; 3KEX; X-ray; 2.80 A; A/B=698-1019.
DR PDB; 3LMG; X-ray; 2.80 A; A/B=684-1020.
DR PDB; 3P11; X-ray; 3.70 A; A=20-532.
DR PDB; 4LEO; X-ray; 2.64 A; C=20-631.
DR PDB; 4P59; X-ray; 3.40 A; A=20-640.
DR PDB; 4RIW; X-ray; 3.10 A; A/C=698-1020.
DR PDB; 4RIX; X-ray; 3.10 A; A/C=698-1020.
DR PDB; 4RIY; X-ray; 2.98 A; A/C=698-1020.
DR PDB; 5CUS; X-ray; 3.20 A; A/B/C/D=20-641.
DR PDB; 5O4O; X-ray; 3.40 A; C=1-643.
DR PDB; 5O7P; X-ray; 4.50 A; C=1-643.
DR PDB; 6KBI; X-ray; 3.00 A; A/B=20-639.
DR PDB; 6OP9; X-ray; 2.50 A; A=674-1001.
DR PDB; 7BHE; X-ray; 2.30 A; B/D=500-643.
DR PDB; 7BHF; X-ray; 2.00 A; B/D=500-630.
DR PDB; 7D85; X-ray; 2.50 A; A/D=328-519.
DR PDB; 7MN5; EM; 2.93 A; A=1-1021.
DR PDB; 7MN6; EM; 3.09 A; A=1-1021.
DR PDB; 7MN8; EM; 3.45 A; A=1-1021.
DR PDBsum; 1M6B; -.
DR PDBsum; 2L9U; -.
DR PDBsum; 3KEX; -.
DR PDBsum; 3LMG; -.
DR PDBsum; 3P11; -.
DR PDBsum; 4LEO; -.
DR PDBsum; 4P59; -.
DR PDBsum; 4RIW; -.
DR PDBsum; 4RIX; -.
DR PDBsum; 4RIY; -.
DR PDBsum; 5CUS; -.
DR PDBsum; 5O4O; -.
DR PDBsum; 5O7P; -.
DR PDBsum; 6KBI; -.
DR PDBsum; 6OP9; -.
DR PDBsum; 7BHE; -.
DR PDBsum; 7BHF; -.
DR PDBsum; 7D85; -.
DR PDBsum; 7MN5; -.
DR PDBsum; 7MN6; -.
DR PDBsum; 7MN8; -.
DR AlphaFoldDB; P21860; -.
DR SMR; P21860; -.
DR BioGRID; 108377; 295.
DR CORUM; P21860; -.
DR DIP; DIP-36441N; -.
DR ELM; P21860; -.
DR IntAct; P21860; 217.
DR MINT; P21860; -.
DR STRING; 9606.ENSP00000267101; -.
DR BindingDB; P21860; -.
DR ChEMBL; CHEMBL5838; -.
DR DrugBank; DB11652; Tucatinib.
DR DrugCentral; P21860; -.
DR GuidetoPHARMACOLOGY; 1798; -.
DR MoonDB; P21860; Predicted.
DR TCDB; 8.A.23.1.39; the basigin (basigin) family.
DR CarbonylDB; P21860; -.
DR GlyConnect; 1711; 5 N-Linked glycans (3 sites).
DR GlyGen; P21860; 10 sites, 5 N-linked glycans (3 sites).
DR iPTMnet; P21860; -.
DR PhosphoSitePlus; P21860; -.
DR BioMuta; ERBB3; -.
DR DMDM; 119534; -.
DR EPD; P21860; -.
DR jPOST; P21860; -.
DR MassIVE; P21860; -.
DR MaxQB; P21860; -.
DR PaxDb; P21860; -.
DR PeptideAtlas; P21860; -.
DR PRIDE; P21860; -.
DR ProteomicsDB; 53934; -. [P21860-1]
DR ProteomicsDB; 53935; -. [P21860-2]
DR ProteomicsDB; 53936; -. [P21860-3]
DR ProteomicsDB; 53937; -. [P21860-4]
DR ProteomicsDB; 53938; -. [P21860-5]
DR ABCD; P21860; 104 sequenced antibodies.
DR Antibodypedia; 3428; 2347 antibodies from 52 providers.
DR CPTC; P21860; 3 antibodies.
DR DNASU; 2065; -.
DR Ensembl; ENST00000267101.8; ENSP00000267101.4; ENSG00000065361.17. [P21860-1]
DR Ensembl; ENST00000411731.6; ENSP00000415753.2; ENSG00000065361.17. [P21860-2]
DR Ensembl; ENST00000415288.6; ENSP00000408340.2; ENSG00000065361.17. [P21860-4]
DR Ensembl; ENST00000551242.5; ENSP00000447510.1; ENSG00000065361.17. [P21860-3]
DR Ensembl; ENST00000683018.1; ENSP00000506822.1; ENSG00000065361.17. [P21860-4]
DR Ensembl; ENST00000683059.1; ENSP00000507402.1; ENSG00000065361.17. [P21860-4]
DR Ensembl; ENST00000683164.1; ENSP00000508051.1; ENSG00000065361.17. [P21860-4]
DR GeneID; 2065; -.
DR KEGG; hsa:2065; -.
DR MANE-Select; ENST00000267101.8; ENSP00000267101.4; NM_001982.4; NP_001973.2.
DR UCSC; uc001sjg.4; human. [P21860-1]
DR CTD; 2065; -.
DR DisGeNET; 2065; -.
DR GeneCards; ERBB3; -.
DR HGNC; HGNC:3431; ERBB3.
DR HPA; ENSG00000065361; Low tissue specificity.
DR MalaCards; ERBB3; -.
DR MIM; 133180; phenotype.
DR MIM; 190151; gene.
DR MIM; 243180; phenotype.
DR MIM; 607598; phenotype.
DR neXtProt; NX_P21860; -.
DR OpenTargets; ENSG00000065361; -.
DR Orphanet; 388; Hirschsprung disease.
DR Orphanet; 137776; Lethal congenital contracture syndrome type 2.
DR PharmGKB; PA27846; -.
DR VEuPathDB; HostDB:ENSG00000065361; -.
DR eggNOG; KOG1025; Eukaryota.
DR GeneTree; ENSGT00940000156107; -.
DR HOGENOM; CLU_003384_3_0_1; -.
DR InParanoid; P21860; -.
DR OMA; THEEVCP; -.
DR OrthoDB; 81952at2759; -.
DR PhylomeDB; P21860; -.
DR TreeFam; TF106002; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P21860; -.
DR Reactome; R-HSA-1227986; Signaling by ERBB2. [P21860-1]
DR Reactome; R-HSA-1236394; Signaling by ERBB4. [P21860-1]
DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling. [P21860-1]
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [P21860-1]
DR Reactome; R-HSA-1306955; GRB7 events in ERBB2 signaling. [P21860-1]
DR Reactome; R-HSA-1358803; Downregulation of ERBB2:ERBB3 signaling. [P21860-1]
DR Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling. [P21860-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. [P21860-1]
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [P21860-1]
DR Reactome; R-HSA-6785631; ERBB2 Regulates Cell Motility. [P21860-1]
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [P21860-1]
DR Reactome; R-HSA-8847993; ERBB2 Activates PTK6 Signaling. [P21860-1]
DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. [P21860-1]
DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. [P21860-1]
DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. [P21860-1]
DR SignaLink; P21860; -.
DR SIGNOR; P21860; -.
DR BioGRID-ORCS; 2065; 83 hits in 1113 CRISPR screens.
DR ChiTaRS; ERBB3; human.
DR EvolutionaryTrace; P21860; -.
DR GeneWiki; ERBB3; -.
DR GenomeRNAi; 2065; -.
DR Pharos; P21860; Tclin.
DR PRO; PR:P21860; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P21860; protein.
DR Bgee; ENSG00000065361; Expressed in trigeminal ganglion and 189 other tissues.
DR ExpressionAtlas; P21860; baseline and differential.
DR Genevisible; P21860; 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:0038143; C:ERBB3:ERBB2 complex; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:BHF-UCL.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
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:0019838; F:growth factor binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0038132; F:neuregulin binding; IDA:UniProtKB.
DR GO; GO:0038131; F:neuregulin receptor activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:BHF-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:CAFA.
DR GO; GO:0021545; P:cranial nerve development; ISS:BHF-UCL.
DR GO; GO:0003197; P:endocardial cushion development; IEA:Ensembl.
DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; IEA:Ensembl.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:BHF-UCL.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:BHF-UCL.
DR GO; GO:0051048; P:negative regulation of secretion; IDA:BHF-UCL.
DR GO; GO:0009968; P:negative regulation of signal transduction; IDA:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:BHF-UCL.
DR GO; GO:0007422; P:peripheral nervous system development; ISS:BHF-UCL.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0055025; P:positive regulation of cardiac muscle tissue development; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; TAS:BHF-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0014037; P:Schwann cell differentiation; ISS:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISS:BHF-UCL.
DR GO; GO:0042060; P:wound healing; NAS:BHF-UCL.
DR CDD; cd00064; FU; 3.
DR Gene3D; 3.80.20.20; -; 2.
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; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/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; 5.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Disease variant; Disulfide bond; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Secreted;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1342
FT /note="Receptor tyrosine-protein kinase erbB-3"
FT /id="PRO_0000016672"
FT TOPO_DOM 20..643
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 644..664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 665..1342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 709..966
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 980..999
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1033..1152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1033..1076
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1111..1132
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 834
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 715..723
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 742
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 788..790
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 834..839
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 686
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 982
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 437
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 469
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 522
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12154198"
FT CARBOHYD 616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..56
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 156..183
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 186..194
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 190..202
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 210..218
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 214..226
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 227..235
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 231..243
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 246..255
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 259..286
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 290..301
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 305..320
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 323..327
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 500..509
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 504..517
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 520..529
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 533..549
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 552..565
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 556..573
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 576..585
FT /evidence="ECO:0000269|PubMed:12154198"
FT DISULFID 589..610
FT /evidence="ECO:0000250"
FT DISULFID 613..621
FT /evidence="ECO:0000250"
FT DISULFID 617..629
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..643
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041661"
FT VAR_SEQ 1..59
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041662"
FT VAR_SEQ 141..183
FT /note="EILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNGRSC -> GQFPM
FT VPSGLTPQPAQDWYLLDDDPRLLTLSASSKVPVTLAAV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7685162"
FT /id="VSP_002893"
FT VAR_SEQ 184..1342
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7685162"
FT /id="VSP_002894"
FT VAR_SEQ 331
FT /note="C -> F (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_041663"
FT VAR_SEQ 332..1342
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_041664"
FT VARIANT 20
FT /note="S -> Y (in dbSNP:rs34379766)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042101"
FT VARIANT 30
FT /note="P -> L (in dbSNP:rs56017157)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042102"
FT VARIANT 104
FT /note="V -> M (in an ovarian mucinous carcinoma sample;
FT somatic mutation; dbSNP:rs1057519893)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042103"
FT VARIANT 204
FT /note="T -> I (in dbSNP:rs56107455)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042104"
FT VARIANT 385
FT /note="N -> S (in dbSNP:rs12320176)"
FT /id="VAR_049710"
FT VARIANT 683
FT /note="R -> W (in dbSNP:rs56387488)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042105"
FT VARIANT 717
FT /note="S -> L (in dbSNP:rs35961836)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042106"
FT VARIANT 744
FT /note="I -> T (in dbSNP:rs55787439)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042107"
FT VARIANT 787
FT /note="T -> P (in VSCN1; 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_086108"
FT VARIANT 873
FT /note="T -> S (in VSCN1; unknown pathological significance;
FT some decrease in ERBB2 phosphorylation upon NG1 treatment,
FT compared to wild-type; does not affect the subcellular
FT localization at the cell membrane)"
FT /evidence="ECO:0000269|PubMed:33497358"
FT /id="VAR_086109"
FT VARIANT 899
FT /note="V -> M (in VSCN1; 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_086110"
FT VARIANT 932
FT /note="Q -> R (in VSCN1; unknown pathological significance;
FT some decrease in ERBB2 phosphorylation upon NG1 treatment,
FT compared to wild-type; does not affect the subcellular
FT localization at the cell membrane)"
FT /evidence="ECO:0000269|PubMed:33497358"
FT /id="VAR_086111"
FT VARIANT 998
FT /note="K -> R (in dbSNP:rs56259600)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042108"
FT VARIANT 1119
FT /note="S -> C (in dbSNP:rs773123)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042109"
FT VARIANT 1127
FT /note="R -> H (in dbSNP:rs2271188)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042110"
FT VARIANT 1177
FT /note="L -> I (in dbSNP:rs55699040)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042111"
FT VARIANT 1254
FT /note="T -> K (in dbSNP:rs55709407)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042112"
FT VARIANT 1271
FT /note="G -> S (in dbSNP:rs11171743)"
FT /id="VAR_049711"
FT VARIANT 1337
FT /note="A -> T (in FERLK; risk factor for erythroleukemia;
FT results in increased ERBB-mediated signaling; results in a
FT block of erythroid differentiation and increased cell
FT proliferation; dbSNP:rs755855285)"
FT /evidence="ECO:0000269|PubMed:27416908"
FT /id="VAR_081641"
FT MUTAGEN 742
FT /note="K->M: Strongly reduced autophosphorylation."
FT /evidence="ECO:0000269|PubMed:20351256"
FT MUTAGEN 868
FT /note="Y->E: Strongly reduced tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:20351256"
FT CONFLICT 560
FT /note="E -> G (in Ref. 2; AAA35979)"
FT /evidence="ECO:0000305"
FT CONFLICT 684
FT /note="G -> S (in Ref. 5; BAF84370)"
FT /evidence="ECO:0000305"
FT CONFLICT 1064
FT /note="E -> G (in Ref. 2; AAA35979)"
FT /evidence="ECO:0000305"
FT CONFLICT 1078
FT /note="C -> S (in Ref. 5; BAG62544)"
FT /evidence="ECO:0000305"
FT CONFLICT 1163
FT /note="D -> G (in Ref. 5; BAF84370)"
FT /evidence="ECO:0000305"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:4LEO"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:7MN5"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:4LEO"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1M6B"
FT HELIX 75..79
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 87..91
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:1M6B"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:4LEO"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:7MN6"
FT STRAND 146..150
FT /evidence="ECO:0007829|PDB:1M6B"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:1M6B"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:1M6B"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:4LEO"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:1M6B"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:7MN5"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:1M6B"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:5CUS"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 235..239
FT /evidence="ECO:0007829|PDB:1M6B"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 243..251
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:1M6B"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 270..274
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 285..289
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 317..322
FT /evidence="ECO:0007829|PDB:1M6B"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:4LEO"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 338..342
FT /evidence="ECO:0007829|PDB:5CUS"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:7D85"
FT HELIX 348..351
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 355..363
FT /evidence="ECO:0007829|PDB:7D85"
FT HELIX 365..369
FT /evidence="ECO:0007829|PDB:7D85"
FT TURN 372..375
FT /evidence="ECO:0007829|PDB:7D85"
FT HELIX 381..389
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 392..395
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:7D85"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:7D85"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 428..433
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 451..457
FT /evidence="ECO:0007829|PDB:7D85"
FT HELIX 465..467
FT /evidence="ECO:0007829|PDB:4LEO"
FT HELIX 470..474
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 481..488
FT /evidence="ECO:0007829|PDB:7D85"
FT HELIX 490..495
FT /evidence="ECO:0007829|PDB:7D85"
FT STRAND 509..513
FT /evidence="ECO:0007829|PDB:7BHF"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 517..522
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 528..531
FT /evidence="ECO:0007829|PDB:7BHE"
FT STRAND 534..540
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 542..545
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 548..551
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 560..562
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 564..569
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 572..581
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 584..588
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 591..595
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 598..604
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 608..612
FT /evidence="ECO:0007829|PDB:7BHF"
FT STRAND 621..625
FT /evidence="ECO:0007829|PDB:7BHF"
FT HELIX 626..628
FT /evidence="ECO:0007829|PDB:7BHF"
FT HELIX 641..670
FT /evidence="ECO:0007829|PDB:2L9U"
FT HELIX 706..708
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 709..717
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 722..728
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 731..733
FT /evidence="ECO:0007829|PDB:3LMG"
FT STRAND 737..744
FT /evidence="ECO:0007829|PDB:6OP9"
FT TURN 747..749
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 753..755
FT /evidence="ECO:0007829|PDB:4RIY"
FT HELIX 758..764
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 774..778
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 780..788
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 795..802
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 803..806
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 808..827
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 837..839
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 840..846
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 848..850
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 856..858
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 865..868
FT /evidence="ECO:0007829|PDB:4RIY"
FT TURN 870..872
FT /evidence="ECO:0007829|PDB:4RIY"
FT HELIX 875..877
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 880..885
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 890..905
FT /evidence="ECO:0007829|PDB:6OP9"
FT TURN 911..914
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 917..919
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 920..925
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 938..947
FT /evidence="ECO:0007829|PDB:6OP9"
FT TURN 952..954
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 958..969
FT /evidence="ECO:0007829|PDB:6OP9"
FT HELIX 972..974
FT /evidence="ECO:0007829|PDB:6OP9"
FT STRAND 980..983
FT /evidence="ECO:0007829|PDB:3KEX"
SQ SEQUENCE 1342 AA; 148098 MW; 7201E7F66CA374BD CRC64;
MRANDALQVL GLLFSLARGS EVGNSQAVCP GTLNGLSVTG DAENQYQTLY KLYERCEVVM
GNLEIVLTGH NADLSFLQWI REVTGYVLVA MNEFSTLPLP NLRVVRGTQV YDGKFAIFVM
LNYNTNSSHA LRQLRLTQLT EILSGGVYIE KNDKLCHMDT IDWRDIVRDR DAEIVVKDNG
RSCPPCHEVC KGRCWGPGSE DCQTLTKTIC APQCNGHCFG PNPNQCCHDE CAGGCSGPQD
TDCFACRHFN DSGACVPRCP QPLVYNKLTF QLEPNPHTKY QYGGVCVASC PHNFVVDQTS
CVRACPPDKM EVDKNGLKMC EPCGGLCPKA CEGTGSGSRF QTVDSSNIDG FVNCTKILGN
LDFLITGLNG DPWHKIPALD PEKLNVFRTV REITGYLNIQ SWPPHMHNFS VFSNLTTIGG
RSLYNRGFSL LIMKNLNVTS LGFRSLKEIS AGRIYISANR QLCYHHSLNW TKVLRGPTEE
RLDIKHNRPR RDCVAEGKVC DPLCSSGGCW GPGPGQCLSC RNYSRGGVCV THCNFLNGEP
REFAHEAECF SCHPECQPME GTATCNGSGS DTCAQCAHFR DGPHCVSSCP HGVLGAKGPI
YKYPDVQNEC RPCHENCTQG CKGPELQDCL GQTLVLIGKT HLTMALTVIA GLVVIFMMLG
GTFLYWRGRR IQNKRAMRRY LERGESIEPL DPSEKANKVL ARIFKETELR KLKVLGSGVF
GTVHKGVWIP EGESIKIPVC IKVIEDKSGR QSFQAVTDHM LAIGSLDHAH IVRLLGLCPG
SSLQLVTQYL PLGSLLDHVR QHRGALGPQL LLNWGVQIAK GMYYLEEHGM VHRNLAARNV
LLKSPSQVQV ADFGVADLLP PDDKQLLYSE AKTPIKWMAL ESIHFGKYTH QSDVWSYGVT
VWELMTFGAE PYAGLRLAEV PDLLEKGERL AQPQICTIDV YMVMVKCWMI DENIRPTFKE
LANEFTRMAR DPPRYLVIKR ESGPGIAPGP EPHGLTNKKL EEVELEPELD LDLDLEAEED
NLATTTLGSA LSLPVGTLNR PRGSQSLLSP SSGYMPMNQG NLGESCQESA VSGSSERCPR
PVSLHPMPRG CLASESSEGH VTGSEAELQE KVSMCRSRSR SRSPRPRGDS AYHSQRHSLL
TPVTPLSPPG LEEEDVNGYV MPDTHLKGTP SSREGTLSSV GLSSVLGTEE EDEDEEYEYM
NRRRRHSPPH PPRPSSLEEL GYEYMDVGSD LSASLGSTQS CPLHPVPIMP TAGTTPDEDY
EYMNRQRDGG GPGGDYAAMG ACPASEQGYE EMRAFQGPGH QAPHVHYARL KTLRSLEATD
SAFDNPDYWH SRLFPKANAQ RT
