GenomeNet

Database: UniProt
Entry: Q02297
LinkDB: Q02297
Original site: Q02297 
ID   NRG1_HUMAN              Reviewed;         640 AA.
AC   Q02297; A5YAK4; A5YAK5; A8K1L2; B7Z4Z3; E9PHH4; O14667; P98202;
AC   Q02298; Q02299; Q07110; Q07111; Q12779; Q12780; Q12781; Q12782;
AC   Q12783; Q12784; Q15491; Q7RTV9; Q7RTW0; Q7RTW1; Q7RTW2; Q8NFN1;
AC   Q8NFN2; Q8NFN3; Q9UPE3;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   10-APR-2019, entry version 219.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 6; 7 AND 8), AND PARTIAL
RP   PROTEIN 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.,
RA   Park J.W., Yansura D., Abadi N., Raab H., Lewis G.D., Shepard H.M.,
RA   Kuang W.-J., 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;
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.,
RA   Meng S.-Y., Lu H.S., Hu S., Chang D., Yang W., Yanigahara D.,
RA   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.,
RA   Kobayashi K., Wroblewski D., Lynch C., Baldasarre M., Hiles I.,
RA   Davis J.B., Hsuan J.J., Totty N.F., Otsu M., McBurney R.N.,
RA   Waterfield M.D., Stroobant P., Gwynne D.;
RT   "Glial growth factors are alternatively spliced erbB2 ligands
RT   expressed in 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
RT   highly 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
RP   VARIANT 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA   Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA   Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA   Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA   DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA   Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA   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.,
RA   O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA   Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA   Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA   Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA   Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA   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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   growth 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.,
RA   Ivarsson O., Chou T.T., Hjaltason O., Birgisdottir B., Jonsson H.,
RA   Gudnadottir V.G., Gudmundsdottir E., Bjornsson A., Ingvarsson B.,
RA   Ingason A., Sigfusson S., Hardardottir H., Harvey R.P., Brunner D.,
RA   Mutel V., Gonzalo A., Lemke G., Sainz J., Johannesson G.,
RA   Andresson T., Gudbjartsson D., Manolescu A., Frigge M.L., Gurney M.E.,
RA   Kong A., Gulcher J.R., Petursson H., 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,
RP   VARIANTS GLN-38 AND THR-289, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP   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.,
RA   Weinberger D.R., Law A.J.;
RT   "Molecular cloning of a brain-specific, developmentally regulated
RT   neuregulin 1 (NRG1) isoform and identification of a functional
RT   promoter 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
RT   project: 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.,
RA   Eppenberger U.;
RL   Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN   [13]
RP   PROTEIN SEQUENCE OF 20-28.
RX   PubMed=7689552;
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.,
RA   Levy R.B., Yarden Y.;
RT   "Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein
RT   that 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
RT   the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell
RT   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
RT   a 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
RT   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
RP   AND 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;
RA   Nagata K., Kohda D., Hatanaka H., Ichikawa S., Matsuda S.,
RA   Yamamoto T., 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
RT   heregulin-alpha.";
RL   Biochemistry 35:3402-3417(1996).
CC   -!- FUNCTION: Direct ligand for ERBB3 and ERBB4 tyrosine kinase
CC       receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors,
CC       resulting in ligand-stimulated tyrosine phosphorylation and
CC       activation of the ERBB receptors. The multiple isoforms perform
CC       diverse functions such as inducing growth and differentiation of
CC       epithelial, glial, neuronal, and skeletal muscle cells; inducing
CC       expression of acetylcholine receptor in synaptic vesicles during
CC       the formation of the neuromuscular junction; stimulating
CC       lobuloalveolar budding and milk production in the mammary gland
CC       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
CC       10 may play a role in motor and sensory neuron development. Binds
CC       to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3
CC       (PubMed:20682778). Acts as a ligand for integrins and binds (via
CC       EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding
CC       to integrins and subsequent ternary complex formation with
CC       integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces
CC       the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and
CC       AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is
CC       essential for the NRG1-mediated activation of these kinases in
CC       neurons (By similarity). {ECO:0000250|UniProtKB:P43322,
CC       ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:1348215,
CC       ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:7902537}.
CC   -!- SUBUNIT: The cytoplasmic domain interacts with the LIM domain
CC       region of LIMK1 (By similarity). Forms a ternary complex with
CC       ERBB3 and ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:20682778).
CC       {ECO:0000250|UniProtKB:P43322, ECO:0000269|PubMed:20682778}.
CC   -!- INTERACTION:
CC       P04626:ERBB2; NbExp=2; IntAct=EBI-2460927, EBI-641062;
CC       P21860:ERBB3; NbExp=3; IntAct=EBI-2460927, EBI-720706;
CC   -!- SUBCELLULAR LOCATION: Pro-neuregulin-1, membrane-bound isoform:
CC       Cell membrane; Single-pass type I membrane protein. Note=Does not
CC       seem to be 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
CC       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
CC         an Ig domain but no glycosylation domain, isoform 9), type III
CC         NRGs (isoforms with a Cys-rich domain, isoform 10) and type IV
CC         NRGs (isoforms with additional 5' exons, isoform 11). All these
CC         isoforms 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         Note=Potential internal signal sequence at positions 76-100.
CC         Variant in position: 46:G->R (in dbSNP:rs3735774). Variant in
CC         position: 127:A->P (in dbSNP:rs34822181).;
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         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Type I isoforms are the predominant forms
CC       expressed in the endocardium. Isoform alpha is expressed in
CC       breast, ovary, testis, prostate, heart, skeletal muscle, lung,
CC       placenta liver, kidney, salivary gland, small intestine and brain,
CC       but not in uterus, stomach, pancreas, and spleen. Isoform 3 is the
CC       predominant form in mesenchymal cells and in non-neuronal organs,
CC       whereas isoform 6 is the major neuronal form. Isoform 8 is
CC       expressed in spinal cord and brain. Isoform 9 is the major form in
CC       skeletal muscle cells; in the nervous system it is expressed in
CC       spinal cord and brain. Also detected in adult heart, placenta,
CC       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
CC       motor neurons. Not detected in adult heart, placenta, lung, liver,
CC       skeletal muscle, kidney, and pancreas. Not expressed in fetal
CC       lung, liver and kidney. Type IV isoforms are brain-specific.
CC       {ECO:0000269|PubMed:17565985}.
CC   -!- DEVELOPMENTAL STAGE: Detectable at early embryonic ages. Isoform
CC       10 is highly expressed in developing spinal motor neurons and in
CC       developing cranial nerve nuclei. Expression is maintained only in
CC       both adult motor neurons and dorsal root ganglion neurons. Type IV
CC       isoforms are expressed in fetal brain.
CC       {ECO:0000269|PubMed:17565985}.
CC   -!- DOMAIN: The cytoplasmic domain may be involved in the regulation
CC       of trafficking and proteolytic processing. Regulation of the
CC       proteolytic processing involves initial intracellular domain
CC       dimerization (By 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
CC       external face leads to the release of the soluble growth factor
CC       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
CC       gamma-heregulin. Translocation t(8;11) with TENM4. The
CC       translocation fuses the 5'-end of TENM4 to NRG1 (isoform 8). The
CC       product of this translocation was first thought to be an
CC       alternatively spliced isoform. Gamma-heregulin is a soluble
CC       activating ligand for the ERBB2-ERBB3 receptor complex and acts as
CC       an autocrine growth factor in a specific breast cancer cell line
CC       (MDA-MB-175). Not detected in breast carcinoma samples, including
CC       ductal, lobular, medullary, and mucinous histological types,
CC       neither in other breast cancer cell lines.
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
CC       - Issue 129 of June 2011;
CC       URL="https://web.expasy.org/spotlight/back_issues/129";
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   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   UniGene; Hs.453951; -.
DR   UniGene; Hs.668810; -.
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   PDBsum; 1HAE; -.
DR   PDBsum; 1HAF; -.
DR   PDBsum; 1HRE; -.
DR   PDBsum; 1HRF; -.
DR   PDBsum; 3U7U; -.
DR   ProteinModelPortal; Q02297; -.
DR   SMR; Q02297; -.
DR   BioGrid; 109332; 71.
DR   CORUM; Q02297; -.
DR   DIP; DIP-355N; -.
DR   IntAct; Q02297; 14.
DR   MINT; Q02297; -.
DR   STRING; 9606.ENSP00000384620; -.
DR   iPTMnet; Q02297; -.
DR   PhosphoSitePlus; Q02297; -.
DR   BioMuta; NRG1; -.
DR   DMDM; 9297018; -.
DR   jPOST; Q02297; -.
DR   MaxQB; Q02297; -.
DR   PaxDb; Q02297; -.
DR   PeptideAtlas; Q02297; -.
DR   PRIDE; Q02297; -.
DR   ProteomicsDB; 58070; -.
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   DNASU; 3084; -.
DR   Ensembl; ENST00000287842; ENSP00000287842; ENSG00000157168. [Q02297-6]
DR   Ensembl; ENST00000356819; ENSP00000349275; ENSG00000157168. [Q02297-7]
DR   Ensembl; ENST00000405005; ENSP00000384620; ENSG00000157168. [Q02297-1]
DR   Ensembl; ENST00000519301; ENSP00000429582; ENSG00000157168. [Q02297-11]
DR   Ensembl; ENST00000520407; ENSP00000434640; ENSG00000157168. [Q02297-9]
DR   Ensembl; ENST00000520502; ENSP00000433289; ENSG00000157168. [Q02297-10]
DR   Ensembl; ENST00000521670; ENSP00000428828; ENSG00000157168. [Q02297-3]
DR   Ensembl; ENST00000523079; ENSP00000430120; ENSG00000157168. [Q02297-12]
DR   GeneID; 3084; -.
DR   KEGG; hsa:3084; -.
DR   UCSC; uc003xip.4; human. [Q02297-1]
DR   CTD; 3084; -.
DR   DisGeNET; 3084; -.
DR   EuPathDB; HostDB:ENSG00000157168.18; -.
DR   GeneCards; NRG1; -.
DR   HGNC; HGNC:7997; NRG1.
DR   HPA; HPA010964; -.
DR   MalaCards; NRG1; -.
DR   MIM; 142445; gene.
DR   neXtProt; NX_Q02297; -.
DR   OpenTargets; ENSG00000157168; -.
DR   PharmGKB; PA31776; -.
DR   eggNOG; ENOG410IEU9; Eukaryota.
DR   eggNOG; ENOG4110ST7; LUCA.
DR   GeneTree; ENSGT00940000157326; -.
DR   HOGENOM; HOG000273863; -.
DR   HOVERGEN; HBG006531; -.
DR   InParanoid; Q02297; -.
DR   KO; K05455; -.
DR   OrthoDB; 313400at2759; -.
DR   PhylomeDB; Q02297; -.
DR   TreeFam; TF332469; -.
DR   Reactome; R-HSA-1227986; Signaling by ERBB2.
DR   Reactome; R-HSA-1236394; Signaling by ERBB4.
DR   Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling.
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.
DR   Reactome; R-HSA-1306955; GRB7 events in ERBB2 signaling.
DR   Reactome; R-HSA-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR   Reactome; R-HSA-1963640; GRB2 events in ERBB2 signaling.
DR   Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling.
DR   Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR   Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-HSA-6785631; ERBB2 Regulates Cell Motility.
DR   Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-HSA-8847993; ERBB2 Activates PTK6 Signaling.
DR   Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling.
DR   Reactome; R-HSA-9620244; Long-term potentiation.
DR   SignaLink; Q02297; -.
DR   SIGNOR; Q02297; -.
DR   ChiTaRS; NRG1; human.
DR   EvolutionaryTrace; Q02297; -.
DR   GeneWiki; Neuregulin_1; -.
DR   GenomeRNAi; 3084; -.
DR   PMAP-CutDB; Q02297; -.
DR   PRO; PR:Q02297; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   Bgee; ENSG00000157168; Expressed in 151 organ(s), highest expression level in oocyte.
DR   ExpressionAtlas; Q02297; baseline and differential.
DR   Genevisible; Q02297; HS.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR   GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR   GO; GO:0099059; C:integral component of presynaptic active zone membrane; IDA:SynGO.
DR   GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR   GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0045499; F:chemorepellent activity; IEA:Ensembl.
DR   GO; GO:0005125; F:cytokine activity; TAS:BHF-UCL.
DR   GO; GO:0005176; F:ErbB-2 class receptor binding; IEA:Ensembl.
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:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; TAS:Reactome.
DR   GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:BHF-UCL.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome.
DR   GO; GO:0005088; F:Ras guanyl-nucleotide exchange factor activity; TAS:Reactome.
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:0000187; P:activation of MAPK activity; IMP: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:0003161; P:cardiac conduction system development; IEA:Ensembl.
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:0000902; P:cell morphogenesis; IEA:Ensembl.
DR   GO; GO:0008283; P:cell population proliferation; IDA:BHF-UCL.
DR   GO; GO:0043624; P:cellular protein complex disassembly; IGI:MGI.
DR   GO; GO:0021842; P:chemorepulsion involved in interneuron migration from the subpallium to the cortex; IEA:Ensembl.
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:0038128; P:ERBB2 signaling pathway; TAS:Reactome.
DR   GO; GO:0038129; P:ERBB3 signaling pathway; IDA:CAFA.
DR   GO; GO:0038130; P:ERBB4 signaling pathway; IDA:UniProtKB.
DR   GO; GO:0021781; P:glial cell fate commitment; IEA:Ensembl.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR   GO; GO:0030879; P:mammary gland development; TAS:BHF-UCL.
DR   GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR   GO; GO:0022011; P:myelination in peripheral nervous system; IEA:Ensembl.
DR   GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IDA:BHF-UCL.
DR   GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IDA:BHF-UCL.
DR   GO; GO:2001223; P:negative regulation of neuron migration; IEA:Ensembl.
DR   GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR   GO; GO:0051048; P:negative regulation of secretion; IDA:BHF-UCL.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
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:0048663; P:neuron fate commitment; IEA:Ensembl.
DR   GO; GO:0045213; P:neurotransmitter receptor metabolic process; IEA:Ensembl.
DR   GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR   GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IEA:Ensembl.
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:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR   GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; TAS:Reactome.
DR   GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IEA:Ensembl.
DR   GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; ISS:BHF-UCL.
DR   GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IEA:Ensembl.
DR   GO; GO:2000145; P:regulation of cell motility; TAS:Reactome.
DR   GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO.
DR   GO; GO:0043497; P:regulation of protein heterodimerization activity; IDA:BHF-UCL.
DR   GO; GO:0043496; P:regulation of protein homodimerization activity; TAS:BHF-UCL.
DR   GO; GO:0007416; P:synapse assembly; IEA:Ensembl.
DR   GO; GO:0099560; P:synaptic membrane adhesion; IDA:SynGO.
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   Gene3D; 2.60.40.10; -; 1.
DR   InterPro; IPR013032; EGF-like_CS.
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; PTHR11100; 1.
DR   PANTHER; PTHR11100:SF7; PTHR11100:SF7; 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; SSF48726; SSF48726; 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.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane;
KW   Chromosomal rearrangement; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Growth factor; Immunoglobulin domain; Membrane; Nucleus;
KW   Polymorphism; Reference proteome; Secreted; Transmembrane;
KW   Transmembrane helix.
FT   PROPEP        1     19       {ECO:0000269|PubMed:7689552}.
FT                                /FTId=PRO_0000019462.
FT   CHAIN        20    640       Pro-neuregulin-1, membrane-bound isoform.
FT                                /FTId=PRO_0000019463.
FT   CHAIN        20    241       Neuregulin-1.
FT                                /FTId=PRO_0000019464.
FT   TOPO_DOM     20    242       Extracellular. {ECO:0000255}.
FT   TRANSMEM    243    265       Helical; Note=Internal signal sequence.
FT                                {ECO:0000255}.
FT   TOPO_DOM    266    640       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       37    128       Ig-like C2-type.
FT   DOMAIN      178    222       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   COMPBIAS    165    177       Ser/Thr-rich.
FT   SITE         34     34       Breakpoint for translocation to form
FT                                gamma-heregulin.
FT   CARBOHYD    120    120       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    126    126       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    164    164       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     57    112       {ECO:0000250}.
FT   DISULFID    182    196       {ECO:0000269|PubMed:8639490}.
FT   DISULFID    190    210       {ECO:0000269|PubMed:8639490}.
FT   DISULFID    212    221       {ECO:0000269|PubMed:8639490}.
FT   VAR_SEQ       1    166       Missing (in isoform 10).
FT                                {ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:7782315}.
FT                                /FTId=VSP_037562.
FT   VAR_SEQ       1     33       MSERKEGRGKGKGKKKERGSGKKPESAAGSQSP -> MRWR
FT                                RAPRRSGRPGPRAQRPGSAARSSPPLPLLPLLLLLGTAALA
FT                                PGAAAGNEAAPAGASVCYSSPPSVGSVQELAQRAAVVIEGK
FT                                VHPQRRQQGALDRKAAAAAGEAGAWGGDREPPAAGPRALGP
FT                                PAEEPLLAANGTVPSWPTAPVPSAGEPGEEAPYLVKVHQVW
FT                                AVKAGGLKKDSLLTVRLGTWGHPAFPSCGRLKEDSRYIFFM
FT                                EPDANSTSRAPAAFRASFPPLETGRNLKKEVSRVLCKRC
FT                                (in isoform 9).
FT                                {ECO:0000303|PubMed:8096067}.
FT                                /FTId=VSP_003425.
FT   VAR_SEQ       1     21       Missing (in isoform 11).
FT                                {ECO:0000303|PubMed:17565985}.
FT                                /FTId=VSP_037563.
FT   VAR_SEQ      22     33       KKPESAAGSQSP -> MGKGRAGRVGTT (in isoform
FT                                11). {ECO:0000303|PubMed:17565985}.
FT                                /FTId=VSP_037564.
FT   VAR_SEQ     134    168       EIITGMPASTEGAYVSSESPIRISVSTEGANTSSS -> A
FT                                (in isoform 9 and isoform 11).
FT                                {ECO:0000303|PubMed:17565985,
FT                                ECO:0000303|PubMed:8096067}.
FT                                /FTId=VSP_003426.
FT   VAR_SEQ     167    167       S -> MEIYSPDMSEVAAERSSSPSTQLSADPSLDGLPAAE
FT                                DMPEPQTEDGRTPGLVGLAVPCCACLEAERLRGCLNSEKIC
FT                                IVPILACLVSLCLCIAGLKWVFVDKIFEYDSPTHLDPGGLG
FT                                QDPIISLDATAASAVWVSSEAYTSPVSRAQSESEVQVTVQG
FT                                DKAVVSFEPSAAPTPKNRIFAFSFLPSTAPSFPSPTRNPEV
FT                                RTPKSATQPQTTETNLQTAPKL (in isoform 10).
FT                                {ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:7782315}.
FT                                /FTId=VSP_037565.
FT   VAR_SEQ     213    241       QPGFTGARCTENVPMKVQNQEKAEELYQK -> PNEFTGDR
FT                                CQNYVMASFYSTSTPFLSLPE (in isoform 8,
FT                                isoform 9 and isoform 10).
FT                                {ECO:0000303|PubMed:1350381,
FT                                ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:7509448,
FT                                ECO:0000303|PubMed:7782315,
FT                                ECO:0000303|PubMed:8096067}.
FT                                /FTId=VSP_003429.
FT   VAR_SEQ     213    234       QPGFTGARCTENVPMKVQNQEK -> PNEFTGDRCQNYVMA
FT                                SFYKHLGIEFME (in isoform 6 and isoform
FT                                11). {ECO:0000303|PubMed:1350381,
FT                                ECO:0000303|PubMed:17565985,
FT                                ECO:0000303|PubMed:7509448}.
FT                                /FTId=VSP_003428.
FT   VAR_SEQ     213    233       QPGFTGARCTENVPMKVQNQE -> PNEFTGDRCQNYVMAS
FT                                FY (in isoform 7 and isoform 12).
FT                                {ECO:0000303|PubMed:1350381,
FT                                ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:7509448}.
FT                                /FTId=VSP_003427.
FT   VAR_SEQ     234    247       KAEELYQKRVLTIT -> SAQMSLLVIAAKTT (in
FT                                isoform 4). {ECO:0000303|PubMed:7509448}.
FT                                /FTId=VSP_003432.
FT   VAR_SEQ     234    234       K -> KHLGIEFIE (in isoform 2).
FT                                {ECO:0000303|PubMed:7509448}.
FT                                /FTId=VSP_003431.
FT   VAR_SEQ     242    640       Missing (in isoform 8, isoform 9 and
FT                                isoform 10). {ECO:0000303|PubMed:1350381,
FT                                ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:7509448,
FT                                ECO:0000303|PubMed:7782315,
FT                                ECO:0000303|PubMed:8096067}.
FT                                /FTId=VSP_003430.
FT   VAR_SEQ     248    640       Missing (in isoform 4).
FT                                {ECO:0000303|PubMed:7509448}.
FT                                /FTId=VSP_003433.
FT   VAR_SEQ     424    640       Missing (in isoform 12).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_046417.
FT   VAR_SEQ     424    462       YVSAMTTPARMSPVDFHTPSSPKSPPSEMSPPVSSMTVS
FT                                -> HNLIAELRRNKAHRSKCMQIQLSATHLRSSSIPHLGFI
FT                                L (in isoform 3).
FT                                {ECO:0000303|PubMed:7509448}.
FT                                /FTId=VSP_003434.
FT   VAR_SEQ     463    640       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:7509448}.
FT                                /FTId=VSP_003435.
FT   VARIANT      38     38       R -> Q (in dbSNP:rs3924999).
FT                                {ECO:0000269|PubMed:17565985}.
FT                                /FTId=VAR_009307.
FT   VARIANT     289    289       M -> T (in dbSNP:rs10503929).
FT                                {ECO:0000269|PubMed:14702039,
FT                                ECO:0000269|PubMed:17565985}.
FT                                /FTId=VAR_053531.
FT   VARIANT     463    463       M -> K.
FT                                /FTId=VAR_009308.
FT   MUTAGEN     181    181       K->E: Defective in integrin-binding and
FT                                in inducing ERBB3 phosphorylation; when
FT                                associated with or without E-185 or E-
FT                                187. No effect on ERBB3-binding,
FT                                defective in integrin-binding and in
FT                                ternary complex formation with ERBB3 and
FT                                integrins, and defective in inducing
FT                                NRG1-ERBB signaling; when associated with
FT                                E-185 and E-187.
FT                                {ECO:0000269|PubMed:20682778}.
FT   MUTAGEN     185    185       K->E: Defective in integrin-binding and
FT                                in inducing ERBB3 phosphorylation; when
FT                                associated with or without E-181 or E-
FT                                187. No effect on ERBB3-binding,
FT                                defective in integrin-binding and in
FT                                ternary complex formation with ERBB3 and
FT                                integrins, and defective in inducing
FT                                NRG1-ERBB signaling; when associated with
FT                                E-181 and E-187.
FT                                {ECO:0000269|PubMed:20682778}.
FT   MUTAGEN     187    187       K->E: Defective in integrin-binding and
FT                                in inducing ERBB3 phosphorylation; when
FT                                associated with or without E-181 or E-
FT                                185. No effect on ERBB3-binding,
FT                                defective in integrin-binding and in
FT                                ternary complex formation with ERBB3 and
FT                                integrins, and defective in inducing
FT                                NRG1-ERBB signaling; when associated with
FT                                E-181 and E-185.
FT                                {ECO:0000269|PubMed:20682778}.
FT   CONFLICT     94     94       K -> A (in Ref. 2; AAA19953).
FT                                {ECO:0000305}.
FT   CONFLICT    107    107       S -> P (in Ref. 10; ABQ53539).
FT                                {ECO:0000305}.
FT   CONFLICT    261    261       V -> L (in Ref. 10; ABQ53540).
FT                                {ECO:0000305}.
FT   CONFLICT    414    414       S -> F (in Ref. 2; AAA19953).
FT                                {ECO:0000305}.
FT   CONFLICT    535    535       Q -> R (in Ref. 2; AAA19951).
FT                                {ECO:0000305}.
FT   STRAND      179    181       {ECO:0000244|PDB:3U7U}.
FT   TURN        185    189       {ECO:0000244|PDB:3U7U}.
FT   STRAND      190    193       {ECO:0000244|PDB:1HRE}.
FT   STRAND      195    199       {ECO:0000244|PDB:3U7U}.
FT   STRAND      200    204       {ECO:0000244|PDB:1HRE}.
FT   STRAND      208    212       {ECO:0000244|PDB:3U7U}.
FT   STRAND      216    218       {ECO:0000244|PDB:3U7U}.
FT   STRAND      233    235       {ECO:0000244|PDB:1HAF}.
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
//
DBGET integrated database retrieval system