ID NRG1_HUMAN Reviewed; 640 AA. AC Q02297; A5YAK4; A5YAK5; A8K1L2; B7Z4Z3; E9PHH4; O14667; P98202; Q02298; AC Q02299; Q07110; Q07111; Q12779; Q12780; Q12781; Q12782; Q12783; Q12784; AC Q15491; Q7RTV9; Q7RTW0; Q7RTW1; Q7RTW2; Q8NFN1; Q8NFN2; Q8NFN3; Q9UPE3; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 247. DE RecName: Full=Pro-neuregulin-1, membrane-bound isoform; DE Short=Pro-NRG1; DE Contains: DE RecName: Full=Neuregulin-1; DE AltName: Full=Acetylcholine receptor-inducing activity; DE Short=ARIA; DE AltName: Full=Breast cancer cell differentiation factor p45; DE AltName: Full=Glial growth factor; DE AltName: Full=Heregulin; DE Short=HRG; DE AltName: Full=Neu differentiation factor; DE AltName: Full=Sensory and motor neuron-derived factor; DE Flags: Precursor; GN Name=NRG1; Synonyms=GGF, HGL, HRGA, NDF, SMDF; 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] (ISOFORMS 1; 6; 7 AND 8), AND PARTIAL PROTEIN RP SEQUENCE. RX PubMed=1350381; DOI=10.1126/science.256.5060.1205; RA Holmes W.E., Sliwkowski M.X., Akita R.W., Henzel W.J., Lee J., Park J.W., RA Yansura D., Abadi N., Raab H., Lewis G.D., Shepard H.M., Kuang W.-J., RA Wood W.I., Goeddel D.V., Vandlen R.L.; RT "Identification of heregulin, a specific activator of p185erbB2."; RL Science 256:1205-1210(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 6; 7 AND 8). RC TISSUE=Kidney adenocarcinoma, and Pituitary; RX PubMed=7509448; DOI=10.1128/mcb.14.3.1909-1919.1994; RA Wen D., Suggs S.V., Karunagaran D., Liu N., Cupples R.L., Luo Y., RA Janssen A.M., Ben-Baruch N., Trollinger D.B., Jacobsen V.L., Meng S.-Y., RA Lu H.S., Hu S., Chang D., Yang W., Yanigahara D., Koski R.A., Yarden Y.; RT "Structural and functional aspects of the multiplicity of Neu RT differentiation factors."; RL Mol. Cell. Biol. 14:1909-1919(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 8 AND 9). RC TISSUE=Brain; RX PubMed=8096067; DOI=10.1038/362312a0; RA Marchionni M.A., Goodearl A.D.J., Chen M.S., Bermingham-McDonogh O., RA Kirk C., Hendricks M., Danehy F., Misumi D., Sudhalter J., Kobayashi K., RA Wroblewski D., Lynch C., Baldasarre M., Hiles I., Davis J.B., Hsuan J.J., RA Totty N.F., Otsu M., McBurney R.N., Waterfield M.D., Stroobant P., RA Gwynne D.; RT "Glial growth factors are alternatively spliced erbB2 ligands expressed in RT the nervous system."; RL Nature 362:312-318(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10). RC TISSUE=Brain stem, and Cerebellum; RX PubMed=7782315; DOI=10.1074/jbc.270.24.14523; RA Ho W.-H., Armanini M.P., Nuijens A., Phillips H.S., Osheroff P.L.; RT "Sensory and motor neuron-derived factor. A novel heregulin variant highly RT expressed in sensory and motor neurons."; RL J. Biol. Chem. 270:14523-14532(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 10 AND 12), AND VARIANT RP THR-289. RC TISSUE=Hippocampus; 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=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF GAMMA-HEREGULIN FUSION PROTEIN. RC TISSUE=Mammary cancer; RX PubMed=9333014; DOI=10.1038/sj.onc.1201317; RA Schaefer G., Fitzpatrick V.D., Sliwkowski M.X.; RT "Gamma-heregulin: a novel heregulin isoform that is an autocrine growth RT factor for the human breast cancer cell line, MDA-MB-175."; RL Oncogene 15:1385-1394(1997). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 3; 8 AND 9), AND RP SUSCEPTIBILITY TO SCHIZOPHRENIA. RX PubMed=12145742; DOI=10.1086/342734; RA Stefansson H., Sigurdsson E., Steinthorsdottir V., Bjornsdottir S., RA Sigmundsson T., Ghosh S., Brynjolfsson J., Gunnarsdottir S., Ivarsson O., RA Chou T.T., Hjaltason O., Birgisdottir B., Jonsson H., Gudnadottir V.G., RA Gudmundsdottir E., Bjornsson A., Ingvarsson B., Ingason A., Sigfusson S., RA Hardardottir H., Harvey R.P., Brunner D., Mutel V., Gonzalo A., Lemke G., RA Sainz J., Johannesson G., Andresson T., Gudbjartsson D., Manolescu A., RA Frigge M.L., Gurney M.E., Kong A., Gulcher J.R., Petursson H., RA Stefansson K.; RT "Neuregulin 1 and susceptibility to Schizophrenia."; RL Am. J. Hum. Genet. 71:877-892(2002). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11), ALTERNATIVE SPLICING, VARIANTS RP GLN-38 AND THR-289, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=Hippocampus, and Prefrontal cortex; RX PubMed=17565985; DOI=10.1074/jbc.m702953200; RA Tan W., Wang Y., Gold B., Chen J., Dean M., Harrison P.J., Weinberger D.R., RA Law A.J.; RT "Molecular cloning of a brain-specific, developmentally regulated RT neuregulin 1 (NRG1) isoform and identification of a functional promoter RT variant associated with schizophrenia."; RL J. Biol. Chem. 282:24343-24351(2007). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 10). RC TISSUE=Brain, and Duodenum; 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 [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-211 (ISOFORM 1). RA Schoumacher F., Herzer S., Flury N., Kueng W., Mueller H., Eppenberger U.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [13] RP PROTEIN SEQUENCE OF 20-28. RX PubMed=7689552; DOI=10.1016/s0021-9258(17)46636-1; RA Culouscou J.-M., Plowman G.D., Carlton G.W., Green J.M., Shoyab M.; RT "Characterization of a breast cancer cell differentiation factor that RT specifically activates the HER4/p180erbB4 receptor."; RL J. Biol. Chem. 268:18407-18410(1993). RN [14] RP PARTIAL PROTEIN SEQUENCE (ISOFORM 1), FUNCTION, AND GLYCOSYLATION. RX PubMed=1348215; DOI=10.1016/0092-8674(92)90131-u; RA Peles E., Bacus S.S., Koski R.A., Lu H.S., Wen D., Ogden S.G., Levy R.B., RA Yarden Y.; RT "Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that RT induces differentiation of mammary tumor cells."; RL Cell 69:205-216(1992). RN [15] RP BINDING TO ERBB4, AND FUNCTION. RX PubMed=7902537; DOI=10.1038/366473a0; RA Plowman G.D., Green J.M., Culouscou J.M., Carlton G.W., Rothwell V.M., RA Buckley S.; RT "Heregulin induces tyrosine phosphorylation of HER4/p180erbB4."; RL Nature 366:473-475(1993). RN [16] RP CHROMOSOMAL TRANSLOCATION. RX PubMed=10523851; DOI=10.1038/sj.onc.1202950; RA Wang X.-Z., Jolicoeur E.M., Conte N., Chaffanet M., Zhang Y., RA Mozziconacci M.-J., Feiner H., Birnbaum D., Pebusque M.-J., Ron D.; RT "Gamma-heregulin is the product of a chromosomal translocation fusing the RT DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell line."; RL Oncogene 18:5718-5721(1999). RN [17] RP CHROMOSOMAL TRANSLOCATION. RX PubMed=10597312; DOI=10.1038/sj.onc.1203136; RA Liu X., Baker E., Eyre H.J., Sutherland G.R., Zhou M.; RT "Gamma-heregulin: a fusion gene of DOC-4 and neuregulin-1 derived from a RT chromosome translocation."; RL Oncogene 18:7110-7114(1999). RN [18] RP BINDING TO ERBB4. RX PubMed=10867024; DOI=10.1074/jbc.c901015199; RA Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C., RA Carraway K.L. III; RT "Ligand discrimination in signaling through an ErbB4 receptor homodimer."; RL J. Biol. Chem. 275:19803-19807(2000). RN [19] RP FUNCTION, BINDING TO ERBB3 AND INTEGRINS, IDENTIFICATION IN A TERNARY RP COMPLEX WITH ERBB3 AND INTEGRINS, AND MUTAGENESIS OF LYS-181; LYS-185 AND RP LYS-187. 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 [20] RP STRUCTURE BY NMR OF 175-241 (ISOFORM 1). RX PubMed=8062828; DOI=10.1002/j.1460-2075.1994.tb06658.x; RA Nagata K., Kohda D., Hatanaka H., Ichikawa S., Matsuda S., Yamamoto T., RA Suzuki A., Inagaki F.; RT "Solution structure of the epidermal growth factor-like domain of RT heregulin-alpha, a ligand for p180erbB-4."; RL EMBO J. 13:3517-3523(1994). RN [21] RP STRUCTURE BY NMR OF 177-239 (ISOFORM 1), AND DISULFIDE BONDS. RX PubMed=8639490; DOI=10.1021/bi952626l; RA Jacobsen N.E., Abadi N., Sliwkowski M.X., Reilly D., Skelton N.J., RA Fairbrother W.J.; RT "High-resolution solution structure of the EGF-like domain of heregulin- RT alpha."; RL Biochemistry 35:3402-3417(1996). CC -!- FUNCTION: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. CC Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in CC ligand-stimulated tyrosine phosphorylation and activation of the ERBB CC receptors. The multiple isoforms perform diverse functions such as CC inducing growth and differentiation of epithelial, glial, neuronal, and CC skeletal muscle cells; inducing expression of acetylcholine receptor in CC synaptic vesicles during the formation of the neuromuscular junction; CC stimulating lobuloalveolar budding and milk production in the mammary CC gland and inducing differentiation of mammary tumor cells; stimulating CC Schwann cell proliferation; implication in the development of the CC myocardium such as trabeculation of the developing heart. Isoform 10 CC may play a role in motor and sensory neuron development. Binds to ERBB4 CC (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). CC Acts as a ligand for integrins and binds (via EGF domain) to integrins CC ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent CC ternary complex formation with integrins and ERRB3 are essential for CC NRG1-ERBB signaling. Induces the phosphorylation and activation of CC MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent CC ERBB4 endocytosis is essential for the NRG1-mediated activation of CC these kinases in neurons (By similarity). CC {ECO:0000250|UniProtKB:P43322, ECO:0000269|PubMed:10867024, CC ECO:0000269|PubMed:1348215, ECO:0000269|PubMed:20682778, CC ECO:0000269|PubMed:7902537}. CC -!- SUBUNIT: The cytoplasmic domain interacts with the LIM domain region of CC LIMK1 (By similarity). Forms a ternary complex with ERBB3 and CC ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:20682778). Interacts with NRDC and CC BACE1 (By similarity). {ECO:0000250|UniProtKB:P43322, CC ECO:0000250|UniProtKB:Q6DR98, ECO:0000269|PubMed:20682778}. CC -!- INTERACTION: CC Q02297-6; P21860: ERBB3; NbExp=2; IntAct=EBI-15651799, EBI-720706; CC Q02297-6; Q15303: ERBB4; NbExp=3; IntAct=EBI-15651799, EBI-80371; CC Q02297-7; P04626: ERBB2; NbExp=2; IntAct=EBI-2460927, EBI-641062; CC Q02297-7; P21860: ERBB3; NbExp=3; IntAct=EBI-2460927, EBI-720706; CC Q02297-10; P07307-3: ASGR2; NbExp=3; IntAct=EBI-12842334, EBI-12808270; CC Q02297-10; P21854: CD72; NbExp=3; IntAct=EBI-12842334, EBI-307924; CC Q02297-10; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-12842334, EBI-10266796; CC Q02297-10; Q86VI4: LAPTM4B; NbExp=3; IntAct=EBI-12842334, EBI-3267258; CC Q02297-10; Q96JQ5: MS4A4A; NbExp=3; IntAct=EBI-12842334, EBI-12820341; CC Q02297-10; P60201-2: PLP1; NbExp=3; IntAct=EBI-12842334, EBI-12188331; CC Q02297-10; Q969K7: TMEM54; NbExp=3; IntAct=EBI-12842334, EBI-3922833; CC -!- SUBCELLULAR LOCATION: [Pro-neuregulin-1, membrane-bound isoform]: Cell CC membrane; Single-pass type I membrane protein. Note=Does not seem to be CC active. CC -!- SUBCELLULAR LOCATION: [Neuregulin-1]: Secreted. CC -!- SUBCELLULAR LOCATION: [Isoform 8]: Nucleus. Note=May be nuclear. CC -!- SUBCELLULAR LOCATION: [Isoform 9]: Secreted. Note=Has a signal peptide. CC -!- SUBCELLULAR LOCATION: [Isoform 10]: Membrane; Single-pass type I CC membrane protein. Note=May possess an internal uncleaved signal CC sequence. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=11; CC Comment=Additional isoforms seem to exist. Isoforms have been CC classified as type I NRGs (isoforms with an Ig domain and a CC glycosylation domain, isoforms 1-8), type II NRGs (isoforms with an CC Ig domain but no glycosylation domain, isoform 9), type III NRGs CC (isoforms with a Cys-rich domain, isoform 10) and type IV NRGs CC (isoforms with additional 5' exons, isoform 11). All these isoforms CC perform distinct tissue-specific functions.; CC Name=1; Synonyms=Alpha; CC IsoId=Q02297-1; Sequence=Displayed; CC Name=2; Synonyms=Alpha1A; CC IsoId=Q02297-2; Sequence=VSP_003431; CC Name=3; Synonyms=Alpha2B; CC IsoId=Q02297-3; Sequence=VSP_003434, VSP_003435; CC Name=4; Synonyms=Alpha3; CC IsoId=Q02297-4; Sequence=VSP_003432, VSP_003433; CC Name=6; Synonyms=Beta1, Beta1A; CC IsoId=Q02297-6; Sequence=VSP_003428; CC Name=7; Synonyms=Beta2; CC IsoId=Q02297-7; Sequence=VSP_003427; CC Name=8; Synonyms=Beta3, GGFHFB1; CC IsoId=Q02297-8; Sequence=VSP_003429, VSP_003430; CC Name=9; Synonyms=GGF2, GGFHPP2; CC IsoId=Q02297-9; Sequence=VSP_003425, VSP_003426, VSP_003429, CC VSP_003430; CC Name=10; Synonyms=SMDF; CC IsoId=Q02297-10; Sequence=VSP_037562, VSP_037565, VSP_003429, CC VSP_003430; CC Name=11; Synonyms=Type IV-beta1a; CC IsoId=Q02297-11; Sequence=VSP_037563, VSP_037564, VSP_003426, CC VSP_003428; CC Name=12; CC IsoId=Q02297-12; Sequence=VSP_003427, VSP_046417; CC -!- TISSUE SPECIFICITY: Type I isoforms are the predominant forms expressed CC in the endocardium. Isoform alpha is expressed in breast, ovary, CC testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, CC salivary gland, small intestine and brain, but not in uterus, stomach, CC pancreas, and spleen. Isoform 3 is the predominant form in mesenchymal CC cells and in non-neuronal organs, whereas isoform 6 is the major CC neuronal form. Isoform 8 is expressed in spinal cord and brain. Isoform CC 9 is the major form in skeletal muscle cells; in the nervous system it CC is expressed in spinal cord and brain. Also detected in adult heart, CC placenta, lung, liver, kidney, and pancreas. Isoform 10 is expressed in CC nervous system: spinal cord motor neurons, dorsal root ganglion CC neurons, and brain. Predominant isoform expressed in sensory and motor CC neurons. Not detected in adult heart, placenta, lung, liver, skeletal CC muscle, kidney, and pancreas. Not expressed in fetal lung, liver and CC kidney. Type IV isoforms are brain-specific. CC {ECO:0000269|PubMed:17565985}. CC -!- DEVELOPMENTAL STAGE: Detectable at early embryonic ages. Isoform 10 is CC highly expressed in developing spinal motor neurons and in developing CC cranial nerve nuclei. Expression is maintained only in both adult motor CC neurons and dorsal root ganglion neurons. Type IV isoforms are CC expressed in fetal brain. {ECO:0000269|PubMed:17565985}. CC -!- DOMAIN: The cytoplasmic domain may be involved in the regulation of CC trafficking and proteolytic processing. Regulation of the proteolytic CC processing involves initial intracellular domain dimerization (By CC similarity). {ECO:0000250}. CC -!- DOMAIN: ERBB receptor binding is elicited entirely by the EGF-like CC domain. CC -!- PTM: Proteolytic cleavage close to the plasma membrane on the external CC face leads to the release of the soluble growth factor form. CC -!- PTM: N- and O-glycosylated. Extensive glycosylation precedes the CC proteolytic cleavage (By similarity). {ECO:0000250}. CC -!- DISEASE: Note=A chromosomal aberration involving NRG1 produces gamma- CC heregulin. Translocation t(8;11) with TENM4. The translocation fuses CC the 5'-end of TENM4 to NRG1 (isoform 8). The product of this CC translocation was first thought to be an alternatively spliced isoform. CC Gamma-heregulin is a soluble activating ligand for the ERBB2-ERBB3 CC receptor complex and acts as an autocrine growth factor in a specific CC breast cancer cell line (MDA-MB-175). Not detected in breast carcinoma CC samples, including ductal, lobular, medullary, and mucinous CC histological types, neither in other breast cancer cell lines. CC -!- MISCELLANEOUS: [Isoform 10]: Potential internal signal sequence at CC positions 76-100. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the neuregulin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA19955.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; CC Sequence=AAC51756.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Tipping the mind - Issue 129 CC of June 2011; CC URL="https://web.expasy.org/spotlight/back_issues/129"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M94165; AAA58638.1; -; mRNA. DR EMBL; M94166; AAA58639.1; -; mRNA. DR EMBL; M94167; AAA58640.1; -; mRNA. DR EMBL; M94168; AAA58641.1; -; mRNA. DR EMBL; U02325; AAA19950.1; -; mRNA. DR EMBL; U02326; AAA19951.1; -; mRNA. DR EMBL; U02327; AAA19952.1; -; mRNA. DR EMBL; U02328; AAA19953.1; -; mRNA. DR EMBL; U02329; AAA19954.1; -; mRNA. DR EMBL; U02330; AAA19955.1; ALT_SEQ; mRNA. DR EMBL; L12260; AAB59622.1; -; mRNA. DR EMBL; L12261; AAB59358.1; -; mRNA. DR EMBL; L41827; AAC41764.1; -; mRNA. DR EMBL; AK289927; BAF82616.1; -; mRNA. DR EMBL; AK298132; BAH12729.1; -; mRNA. DR EMBL; AC021909; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC022833; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC022850; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC023948; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC068359; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC068931; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC083977; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC103675; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104000; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104029; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC113209; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF009227; AAC51756.1; ALT_INIT; mRNA. DR EMBL; AF491780; AAM71137.1; -; Genomic_DNA. DR EMBL; AF491780; AAM71139.1; -; Genomic_DNA. DR EMBL; AF491780; AAM71140.1; -; Genomic_DNA. DR EMBL; EF372273; ABQ53539.1; -; mRNA. DR EMBL; EF372274; ABQ53540.1; -; mRNA. DR EMBL; CH471080; EAW63411.1; -; Genomic_DNA. DR EMBL; BC064587; AAH64587.1; -; mRNA. DR EMBL; BC073871; AAH73871.1; -; mRNA. DR EMBL; AF026146; AAD01795.1; -; mRNA. DR EMBL; BK000383; DAA00044.1; -; Genomic_DNA. DR EMBL; BK000383; DAA00045.1; -; Genomic_DNA. DR EMBL; BK000383; DAA00046.1; -; Genomic_DNA. DR EMBL; BK000383; DAA00047.1; -; Genomic_DNA. DR CCDS; CCDS47836.1; -. [Q02297-9] DR CCDS; CCDS55218.1; -. [Q02297-11] DR CCDS; CCDS55219.1; -. [Q02297-12] DR CCDS; CCDS6083.1; -. [Q02297-6] DR CCDS; CCDS6084.1; -. [Q02297-7] DR CCDS; CCDS6085.1; -. [Q02297-1] DR CCDS; CCDS6086.1; -. [Q02297-3] DR CCDS; CCDS6087.1; -. [Q02297-10] DR CCDS; CCDS94274.1; -. [Q02297-8] DR PIR; A43273; A43273. DR PIR; A56943; A56943. DR PIR; B43273; B43273. DR PIR; C43273; C43273. DR PIR; D43273; D43273. DR PIR; I38403; I38403. DR PIR; I38404; I38404. DR PIR; I38408; I38408. DR PIR; S32357; S32357. DR RefSeq; NP_001153467.1; NM_001159995.2. DR RefSeq; NP_001153471.1; NM_001159999.2. DR RefSeq; NP_001153473.1; NM_001160001.2. [Q02297-11] DR RefSeq; NP_001153477.1; NM_001160005.1. DR RefSeq; NP_001153480.1; NM_001160008.1. [Q02297-12] DR RefSeq; NP_001309134.1; NM_001322205.1. DR RefSeq; NP_001309135.1; NM_001322206.1. DR RefSeq; NP_001309136.1; NM_001322207.1. DR RefSeq; NP_039250.2; NM_013956.4. [Q02297-6] DR RefSeq; NP_039251.2; NM_013957.4. [Q02297-7] DR RefSeq; NP_039252.2; NM_013958.3. [Q02297-8] DR RefSeq; NP_039253.1; NM_013959.3. [Q02297-10] DR RefSeq; NP_039254.1; NM_013960.4. [Q02297-3] DR RefSeq; NP_039256.2; NM_013962.2. [Q02297-9] DR RefSeq; NP_039258.1; NM_013964.4. [Q02297-1] DR PDB; 1HAE; NMR; -; A=177-239. DR PDB; 1HAF; NMR; -; A=177-239. DR PDB; 1HRE; NMR; -; A=175-241. DR PDB; 1HRF; NMR; -; A=175-241. DR PDB; 3U7U; X-ray; 3.03 A; G/H/I/J/K/L=175-212. DR PDB; 7MN5; EM; 2.93 A; H=176-237. DR PDB; 7MN6; EM; 3.09 A; H=176-237. DR PDB; 7MN8; EM; 3.45 A; H=176-237. DR PDB; 7SJL; NMR; -; A=34-133. DR PDBsum; 1HAE; -. DR PDBsum; 1HAF; -. DR PDBsum; 1HRE; -. DR PDBsum; 1HRF; -. DR PDBsum; 3U7U; -. DR PDBsum; 7MN5; -. DR PDBsum; 7MN6; -. DR PDBsum; 7MN8; -. DR PDBsum; 7SJL; -. DR AlphaFoldDB; Q02297; -. DR EMDB; EMD-23916; -. DR EMDB; EMD-23917; -. DR EMDB; EMD-23918; -. DR SMR; Q02297; -. DR BioGRID; 109332; 108. DR CORUM; Q02297; -. DR DIP; DIP-355N; -. DR IntAct; Q02297; 55. DR MINT; Q02297; -. DR STRING; 9606.ENSP00000287842; -. DR GlyCosmos; Q02297; 3 sites, No reported glycans. DR GlyGen; Q02297; 4 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q02297; -. DR PhosphoSitePlus; Q02297; -. DR BioMuta; NRG1; -. DR DMDM; 9297018; -. DR jPOST; Q02297; -. DR MassIVE; Q02297; -. DR MaxQB; Q02297; -. DR PaxDb; 9606-ENSP00000384620; -. DR PeptideAtlas; Q02297; -. DR ProteomicsDB; 20533; -. DR ProteomicsDB; 58070; -. [Q02297-1] DR ProteomicsDB; 58071; -. [Q02297-10] DR ProteomicsDB; 58072; -. [Q02297-11] DR ProteomicsDB; 58073; -. [Q02297-2] DR ProteomicsDB; 58074; -. [Q02297-3] DR ProteomicsDB; 58075; -. [Q02297-4] DR ProteomicsDB; 58076; -. [Q02297-6] DR ProteomicsDB; 58077; -. [Q02297-7] DR ProteomicsDB; 58078; -. [Q02297-8] DR ProteomicsDB; 58079; -. [Q02297-9] DR ABCD; Q02297; 1 sequenced antibody. DR Antibodypedia; 3706; 1142 antibodies from 46 providers. DR DNASU; 3084; -. DR Ensembl; ENST00000287842.7; ENSP00000287842.4; ENSG00000157168.22. [Q02297-6] DR Ensembl; ENST00000356819.7; ENSP00000349275.6; ENSG00000157168.22. [Q02297-7] DR Ensembl; ENST00000405005.8; ENSP00000384620.2; ENSG00000157168.22. [Q02297-1] DR Ensembl; ENST00000519301.6; ENSP00000429582.1; ENSG00000157168.22. [Q02297-11] DR Ensembl; ENST00000520407.5; ENSP00000434640.1; ENSG00000157168.22. [Q02297-9] DR Ensembl; ENST00000520502.7; ENSP00000433289.1; ENSG00000157168.22. [Q02297-10] DR Ensembl; ENST00000521670.5; ENSP00000428828.1; ENSG00000157168.22. [Q02297-3] DR Ensembl; ENST00000523079.5; ENSP00000430120.1; ENSG00000157168.22. [Q02297-12] DR Ensembl; ENST00000650919.1; ENSP00000498811.1; ENSG00000157168.22. [Q02297-8] DR GeneID; 3084; -. DR KEGG; hsa:3084; -. DR MANE-Select; ENST00000405005.8; ENSP00000384620.2; NM_013964.5; NP_039258.1. DR UCSC; uc003xip.4; human. [Q02297-1] DR AGR; HGNC:7997; -. DR CTD; 3084; -. DR DisGeNET; 3084; -. DR GeneCards; NRG1; -. DR HGNC; HGNC:7997; NRG1. DR HPA; ENSG00000157168; Tissue enhanced (liver). DR MalaCards; NRG1; -. DR MIM; 142445; gene. DR neXtProt; NX_Q02297; -. DR OpenTargets; ENSG00000157168; -. DR PharmGKB; PA31776; -. DR VEuPathDB; HostDB:ENSG00000157168; -. DR eggNOG; ENOG502QRUM; Eukaryota. DR GeneTree; ENSGT00940000157326; -. DR HOGENOM; CLU_023628_1_0_1; -. DR InParanoid; Q02297; -. DR OMA; HSWSTGQ; -. DR OrthoDB; 3025258at2759; -. DR PhylomeDB; Q02297; -. DR TreeFam; TF332469; -. DR PathwayCommons; Q02297; -. DR Reactome; R-HSA-1227986; Signaling by ERBB2. [Q02297-10] DR Reactome; R-HSA-1236394; Signaling by ERBB4. [Q02297-10] DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling. [Q02297-10] DR Reactome; R-HSA-1250342; PI3K events in ERBB4 signaling. DR Reactome; R-HSA-1250347; SHC1 events in ERBB4 signaling. DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [Q02297-10] DR Reactome; R-HSA-1306955; GRB7 events in ERBB2 signaling. [Q02297-10] DR Reactome; R-HSA-1358803; Downregulation of ERBB2:ERBB3 signaling. [Q02297-10] DR Reactome; R-HSA-1963640; GRB2 events in ERBB2 signaling. DR Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling. [Q02297-10] DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. [Q02297-10] DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [Q02297-10] DR Reactome; R-HSA-6785631; ERBB2 Regulates Cell Motility. [Q02297-10] DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [Q02297-10] DR Reactome; R-HSA-8847993; ERBB2 Activates PTK6 Signaling. [Q02297-10] DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. [Q02297-10] DR Reactome; R-HSA-9620244; Long-term potentiation. DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. [Q02297-10] DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. [Q02297-10] DR SignaLink; Q02297; -. DR SIGNOR; Q02297; -. DR BioGRID-ORCS; 3084; 12 hits in 1160 CRISPR screens. DR ChiTaRS; NRG1; human. DR EvolutionaryTrace; Q02297; -. DR GeneWiki; Neuregulin_1; -. DR GenomeRNAi; 3084; -. DR Pharos; Q02297; Tbio. DR PRO; PR:Q02297; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q02297; Protein. DR Bgee; ENSG00000157168; Expressed in ventricular zone and 142 other cell types or tissues. DR ExpressionAtlas; Q02297; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central. DR GO; GO:0005125; F:cytokine activity; TAS:BHF-UCL. DR GO; GO:0043125; F:ErbB-3 class receptor binding; IDA:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:BHF-UCL. DR GO; GO:0048018; F:receptor ligand activity; IDA:MGI. DR GO; GO:0030971; F:receptor tyrosine kinase binding; NAS:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL. DR GO; GO:0003712; F:transcription coregulator activity; IDA:MGI. DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; NAS:UniProtKB. DR GO; GO:0032148; P:activation of protein kinase B activity; IMP:UniProtKB. DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; IDA:BHF-UCL. DR GO; GO:0048513; P:animal organ development; IBA:GO_Central. DR GO; GO:0055007; P:cardiac muscle cell differentiation; ISS:BHF-UCL. DR GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; IDA:BHF-UCL. DR GO; GO:0007154; P:cell communication; TAS:BHF-UCL. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0008283; P:cell population proliferation; IDA:BHF-UCL. DR GO; GO:0060956; P:endocardial cell differentiation; IDA:BHF-UCL. DR GO; GO:0038127; P:ERBB signaling pathway; IDA:BHF-UCL. DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; IDA:MGI. DR GO; GO:0038135; P:ERBB2-ERBB4 signaling pathway; IDA:MGI. DR GO; GO:0038129; P:ERBB3 signaling pathway; IDA:CAFA. DR GO; GO:0038130; P:ERBB4 signaling pathway; IDA:UniProtKB. DR GO; GO:0038138; P:ERBB4-ERBB4 signaling pathway; IDA:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0030879; P:mammary gland development; TAS:BHF-UCL. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IDA:BHF-UCL. DR GO; GO:0051048; P:negative regulation of secretion; IDA:BHF-UCL. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0014032; P:neural crest cell development; TAS:BHF-UCL. DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:BHF-UCL. DR GO; GO:0030307; P:positive regulation of cell growth; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; IDA:UniProtKB. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:BHF-UCL. DR GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; ISS:BHF-UCL. DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO. DR GO; GO:0051238; P:sequestering of metal ion; EXP:DisProt. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:BHF-UCL. DR GO; GO:0055012; P:ventricular cardiac muscle cell differentiation; IDA:BHF-UCL. DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IDA:BHF-UCL. DR GO; GO:0042060; P:wound healing; IDA:BHF-UCL. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd05895; Ig_Pro_neuregulin-1; 1. DR DisProt; DP01520; -. [Q02297-10] DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 2.10.25.10; Laminin; 1. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR040180; Neuregulin. DR InterPro; IPR002154; Neuregulin_C. DR InterPro; IPR018250; NRG1. DR PANTHER; PTHR11100; HEREGULIN-NEUREGULIN FAMILY MEMBER; 1. DR PANTHER; PTHR11100:SF7; PRO-NEUREGULIN-1, MEMBRANE-BOUND ISOFORM; 1. DR Pfam; PF00008; EGF; 1. DR Pfam; PF07679; I-set; 1. DR Pfam; PF02158; Neuregulin; 1. DR PRINTS; PR01089; NEUREGULIN. DR SMART; SM00181; EGF; 1. DR SMART; SM00409; IG; 1. DR SMART; SM00408; IGc2; 1. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR PROSITE; PS00022; EGF_1; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR Genevisible; Q02297; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; KW Chromosomal rearrangement; Direct protein sequencing; Disulfide bond; KW EGF-like domain; Glycoprotein; Growth factor; Immunoglobulin domain; KW Membrane; Nucleus; Reference proteome; Secreted; Transmembrane; KW Transmembrane helix. FT PROPEP 1..19 FT /evidence="ECO:0000269|PubMed:7689552" FT /id="PRO_0000019462" FT CHAIN 20..640 FT /note="Pro-neuregulin-1, membrane-bound isoform" FT /id="PRO_0000019463" FT CHAIN 20..241 FT /note="Neuregulin-1" FT /id="PRO_0000019464" FT TOPO_DOM 20..242 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 243..265 FT /note="Helical; Note=Internal signal sequence" FT /evidence="ECO:0000255" FT TOPO_DOM 266..640 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 37..128 FT /note="Ig-like C2-type" FT DOMAIN 178..222 FT /note="EGF-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 1..53 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 334..360 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 375..399 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 433..461 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 524..588 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 375..389 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 559..573 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 34 FT /note="Breakpoint for translocation to form gamma- FT heregulin" FT CARBOHYD 120 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 126 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 164 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 57..112 FT /evidence="ECO:0000250" FT DISULFID 182..196 FT /evidence="ECO:0000269|PubMed:8639490" FT DISULFID 190..210 FT /evidence="ECO:0000269|PubMed:8639490" FT DISULFID 212..221 FT /evidence="ECO:0000269|PubMed:8639490" FT VAR_SEQ 1..166 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7782315" FT /id="VSP_037562" FT VAR_SEQ 1..33 FT /note="MSERKEGRGKGKGKKKERGSGKKPESAAGSQSP -> MRWRRAPRRSGRPGP FT RAQRPGSAARSSPPLPLLPLLLLLGTAALAPGAAAGNEAAPAGASVCYSSPPSVGSVQE FT LAQRAAVVIEGKVHPQRRQQGALDRKAAAAAGEAGAWGGDREPPAAGPRALGPPAEEPL FT LAANGTVPSWPTAPVPSAGEPGEEAPYLVKVHQVWAVKAGGLKKDSLLTVRLGTWGHPA FT FPSCGRLKEDSRYIFFMEPDANSTSRAPAAFRASFPPLETGRNLKKEVSRVLCKRC FT (in isoform 9)" FT /evidence="ECO:0000303|PubMed:8096067" FT /id="VSP_003425" FT VAR_SEQ 1..21 FT /note="Missing (in isoform 11)" FT /evidence="ECO:0000303|PubMed:17565985" FT /id="VSP_037563" FT VAR_SEQ 22..33 FT /note="KKPESAAGSQSP -> MGKGRAGRVGTT (in isoform 11)" FT /evidence="ECO:0000303|PubMed:17565985" FT /id="VSP_037564" FT VAR_SEQ 134..168 FT /note="EIITGMPASTEGAYVSSESPIRISVSTEGANTSSS -> A (in isoform FT 9 and isoform 11)" FT /evidence="ECO:0000303|PubMed:17565985, FT ECO:0000303|PubMed:8096067" FT /id="VSP_003426" FT VAR_SEQ 167 FT /note="S -> MEIYSPDMSEVAAERSSSPSTQLSADPSLDGLPAAEDMPEPQTEDGR FT TPGLVGLAVPCCACLEAERLRGCLNSEKICIVPILACLVSLCLCIAGLKWVFVDKIFEY FT DSPTHLDPGGLGQDPIISLDATAASAVWVSSEAYTSPVSRAQSESEVQVTVQGDKAVVS FT FEPSAAPTPKNRIFAFSFLPSTAPSFPSPTRNPEVRTPKSATQPQTTETNLQTAPKL FT (in isoform 10)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7782315" FT /id="VSP_037565" FT VAR_SEQ 213..241 FT /note="QPGFTGARCTENVPMKVQNQEKAEELYQK -> PNEFTGDRCQNYVMASFYS FT TSTPFLSLPE (in isoform 8, isoform 9 and isoform 10)" FT /evidence="ECO:0000303|PubMed:1350381, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7509448, ECO:0000303|PubMed:7782315, FT ECO:0000303|PubMed:8096067" FT /id="VSP_003429" FT VAR_SEQ 213..234 FT /note="QPGFTGARCTENVPMKVQNQEK -> PNEFTGDRCQNYVMASFYKHLGIEFM FT E (in isoform 6 and isoform 11)" FT /evidence="ECO:0000303|PubMed:1350381, FT ECO:0000303|PubMed:17565985, ECO:0000303|PubMed:7509448" FT /id="VSP_003428" FT VAR_SEQ 213..233 FT /note="QPGFTGARCTENVPMKVQNQE -> PNEFTGDRCQNYVMASFY (in FT isoform 7 and isoform 12)" FT /evidence="ECO:0000303|PubMed:1350381, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:7509448" FT /id="VSP_003427" FT VAR_SEQ 234..247 FT /note="KAEELYQKRVLTIT -> SAQMSLLVIAAKTT (in isoform 4)" FT /evidence="ECO:0000303|PubMed:7509448" FT /id="VSP_003432" FT VAR_SEQ 234 FT /note="K -> KHLGIEFIE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7509448" FT /id="VSP_003431" FT VAR_SEQ 242..640 FT /note="Missing (in isoform 8, isoform 9 and isoform 10)" FT /evidence="ECO:0000303|PubMed:1350381, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7509448, ECO:0000303|PubMed:7782315, FT ECO:0000303|PubMed:8096067" FT /id="VSP_003430" FT VAR_SEQ 248..640 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:7509448" FT /id="VSP_003433" FT VAR_SEQ 424..640 FT /note="Missing (in isoform 12)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046417" FT VAR_SEQ 424..462 FT /note="YVSAMTTPARMSPVDFHTPSSPKSPPSEMSPPVSSMTVS -> HNLIAELRR FT NKAHRSKCMQIQLSATHLRSSSIPHLGFIL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:7509448" FT /id="VSP_003434" FT VAR_SEQ 463..640 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:7509448" FT /id="VSP_003435" FT VARIANT 38 FT /note="R -> Q (in dbSNP:rs3924999)" FT /evidence="ECO:0000269|PubMed:17565985" FT /id="VAR_009307" FT VARIANT 289 FT /note="M -> T (in dbSNP:rs10503929)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:17565985" FT /id="VAR_053531" FT VARIANT 463 FT /note="M -> K" FT /id="VAR_009308" FT MUTAGEN 181 FT /note="K->E: Defective in integrin-binding and in inducing FT ERBB3 phosphorylation; when associated with or without FT E-185 or E-187. No effect on ERBB3-binding, defective in FT integrin-binding and in ternary complex formation with FT ERBB3 and integrins, and defective in inducing NRG1-ERBB FT signaling; when associated with E-185 and E-187." FT /evidence="ECO:0000269|PubMed:20682778" FT MUTAGEN 185 FT /note="K->E: Defective in integrin-binding and in inducing FT ERBB3 phosphorylation; when associated with or without FT E-181 or E-187. No effect on ERBB3-binding, defective in FT integrin-binding and in ternary complex formation with FT ERBB3 and integrins, and defective in inducing NRG1-ERBB FT signaling; when associated with E-181 and E-187." FT /evidence="ECO:0000269|PubMed:20682778" FT MUTAGEN 187 FT /note="K->E: Defective in integrin-binding and in inducing FT ERBB3 phosphorylation; when associated with or without FT E-181 or E-185. No effect on ERBB3-binding, defective in FT integrin-binding and in ternary complex formation with FT ERBB3 and integrins, and defective in inducing NRG1-ERBB FT signaling; when associated with E-181 and E-185." FT /evidence="ECO:0000269|PubMed:20682778" FT CONFLICT 94 FT /note="K -> A (in Ref. 2; AAA19953)" FT /evidence="ECO:0000305" FT CONFLICT 107 FT /note="S -> P (in Ref. 10; ABQ53539)" FT /evidence="ECO:0000305" FT CONFLICT 261 FT /note="V -> L (in Ref. 10; ABQ53540)" FT /evidence="ECO:0000305" FT CONFLICT 414 FT /note="S -> F (in Ref. 2; AAA19953)" FT /evidence="ECO:0000305" FT CONFLICT 535 FT /note="Q -> R (in Ref. 2; AAA19951)" FT /evidence="ECO:0000305" FT STRAND 45..48 FT /evidence="ECO:0007829|PDB:7SJL" FT STRAND 51..61 FT /evidence="ECO:0007829|PDB:7SJL" FT STRAND 67..72 FT /evidence="ECO:0007829|PDB:7SJL" FT TURN 79..81 FT /evidence="ECO:0007829|PDB:7SJL" FT STRAND 86..91 FT /evidence="ECO:0007829|PDB:7SJL" FT STRAND 94..102 FT /evidence="ECO:0007829|PDB:7SJL" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:7SJL" FT STRAND 108..115 FT /evidence="ECO:0007829|PDB:7SJL" FT STRAND 120..130 FT /evidence="ECO:0007829|PDB:7SJL" FT STRAND 179..181 FT /evidence="ECO:0007829|PDB:3U7U" FT TURN 185..189 FT /evidence="ECO:0007829|PDB:3U7U" FT STRAND 190..193 FT /evidence="ECO:0007829|PDB:1HRE" FT STRAND 195..199 FT /evidence="ECO:0007829|PDB:3U7U" FT STRAND 200..204 FT /evidence="ECO:0007829|PDB:1HRE" FT STRAND 208..212 FT /evidence="ECO:0007829|PDB:3U7U" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:3U7U" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:1HAF" FT VARIANT Q02297-10:46 FT /note="G -> R (in dbSNP:rs3735774)" FT /evidence="ECO:0000305" FT /id="VAR_082866" FT VARIANT Q02297-10:127 FT /note="A -> P (in dbSNP:rs34822181)" FT /evidence="ECO:0000305" FT /id="VAR_082867" SQ SEQUENCE 640 AA; 70392 MW; C30D3F614AADFF62 CRC64; MSERKEGRGK GKGKKKERGS GKKPESAAGS QSPALPPRLK EMKSQESAAG SKLVLRCETS SEYSSLRFKW FKNGNELNRK NKPQNIKIQK KPGKSELRIN KASLADSGEY MCKVISKLGN DSASANITIV ESNEIITGMP ASTEGAYVSS ESPIRISVST EGANTSSSTS TSTTGTSHLV KCAEKEKTFC VNGGECFMVK DLSNPSRYLC KCQPGFTGAR CTENVPMKVQ NQEKAEELYQ KRVLTITGIC IALLVVGIMC VVAYCKTKKQ RKKLHDRLRQ SLRSERNNMM NIANGPHHPN PPPENVQLVN QYVSKNVISS EHIVEREAET SFSTSHYTST AHHSTTVTQT PSHSWSNGHT ESILSESHSV IVMSSVENSR HSSPTGGPRG RLNGTGGPRE CNSFLRHARE TPDSYRDSPH SERYVSAMTT PARMSPVDFH TPSSPKSPPS EMSPPVSSMT VSMPSMAVSP FMEEERPLLL VTPPRLREKK FDHHPQQFSS FHHNPAHDSN SLPASPLRIV EDEEYETTQE YEPAQEPVKK LANSRRAKRT KPNGHIANRL EVDSNTSSQS SNSESETEDE RVGEDTPFLG IQNPLAASLE ATPAFRLADS RTNPAGRFST QEEIQARLSS VIANQDPIAV //