ID   NRG3_MOUSE              Reviewed;         713 AA.
AC   O35181;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   24-JAN-2024, entry version 174.
DE   RecName: Full=Pro-neuregulin-3, membrane-bound isoform;
DE            Short=Pro-NRG3;
DE   Contains:
DE     RecName: Full=Neuregulin-3;
DE              Short=NRG-3;
DE   Flags: Precursor;
GN   Name=Nrg3;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH ERBB4.
RC   TISSUE=Brain;
RX   PubMed=9275162; DOI=10.1073/pnas.94.18.9562;
RA   Zhang D., Sliwkowski M.X., Mark M., Frantz G., Akita R., Sun Y., Hillan K.,
RA   Crowley C., Brush J., Godowski P.J.;
RT   "Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and
RT   activates ErbB4.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:9562-9567(1997).
CC   -!- FUNCTION: Direct ligand for the ERBB4 tyrosine kinase receptor. Binding
CC       results in ligand-stimulated tyrosine phosphorylation and activation of
CC       the receptor. Does not bind to the EGF receptor, ERBB2 or ERBB3
CC       receptors. {ECO:0000269|PubMed:9275162}.
CC   -!- SUBUNIT: Interacts with ERBB4. {ECO:0000269|PubMed:9275162}.
CC   -!- SUBCELLULAR LOCATION: [Pro-neuregulin-3, membrane-bound isoform]: Cell
CC       membrane {ECO:0000250}; Single-pass type I membrane protein
CC       {ECO:0000250}. Note=Does not seem to be active. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Neuregulin-3]: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in sympathetic, motor, and sensory
CC       neurons.
CC   -!- DEVELOPMENTAL STAGE: Detected as early as 11 dpc. At 13 dpc detected
CC       mainly in the nervous system. At 16 dpc, detected in the brain, spinal
CC       cord, trigeminal, vestibular-cochlear, and spinal ganglia. In adults,
CC       expressed in spinal cord, and numerous brain regions.
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. {ECO:0000250}.
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       {ECO:0000250}.
CC   -!- PTM: Extensive glycosylation precedes the proteolytic cleavage.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the neuregulin family. {ECO:0000305}.
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DR   EMBL; AF010130; AAB70914.1; -; mRNA.
DR   CCDS; CCDS26954.1; -.
DR   PIR; T44447; T44447.
DR   RefSeq; NP_032760.1; NM_008734.3.
DR   AlphaFoldDB; O35181; -.
DR   SMR; O35181; -.
DR   STRING; 10090.ENSMUSP00000136884; -.
DR   iPTMnet; O35181; -.
DR   PhosphoSitePlus; O35181; -.
DR   PaxDb; 10090-ENSMUSP00000136884; -.
DR   Antibodypedia; 30013; 265 antibodies from 36 providers.
DR   DNASU; 18183; -.
DR   Ensembl; ENSMUST00000166968.9; ENSMUSP00000136884.2; ENSMUSG00000041014.18.
DR   GeneID; 18183; -.
DR   KEGG; mmu:18183; -.
DR   UCSC; uc007tbz.2; mouse.
DR   AGR; MGI:1097165; -.
DR   CTD; 10718; -.
DR   MGI; MGI:1097165; Nrg3.
DR   VEuPathDB; HostDB:ENSMUSG00000041014; -.
DR   eggNOG; ENOG502QS97; Eukaryota.
DR   GeneTree; ENSGT00940000156754; -.
DR   InParanoid; O35181; -.
DR   OMA; WCKNSCS; -.
DR   OrthoDB; 5355912at2759; -.
DR   PhylomeDB; O35181; -.
DR   TreeFam; TF336537; -.
DR   Reactome; R-MMU-1227986; Signaling by ERBB2.
DR   Reactome; R-MMU-1236394; Signaling by ERBB4.
DR   Reactome; R-MMU-1250196; SHC1 events in ERBB2 signaling.
DR   Reactome; R-MMU-1250342; PI3K events in ERBB4 signaling.
DR   Reactome; R-MMU-1250347; SHC1 events in ERBB4 signaling.
DR   Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-MMU-1963640; GRB2 events in ERBB2 signaling.
DR   Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-MMU-6785631; ERBB2 Regulates Cell Motility.
DR   Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-MMU-8847993; ERBB2 Activates PTK6 Signaling.
DR   Reactome; R-MMU-8863795; Downregulation of ERBB2 signaling.
DR   BioGRID-ORCS; 18183; 4 hits in 77 CRISPR screens.
DR   ChiTaRS; Nrg3; mouse.
DR   PRO; PR:O35181; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; O35181; Protein.
DR   Bgee; ENSMUSG00000041014; Expressed in lateral mesenchyme derived from mesoderm and 88 other cell types or tissues.
DR   ExpressionAtlas; O35181; baseline and differential.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IDA:SynGO.
DR   GO; GO:0045499; F:chemorepellent activity; IDA:MGI.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0048018; F:receptor ligand activity; IPI:MGI.
DR   GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR   GO; GO:0021842; P:chemorepulsion involved in interneuron migration from the subpallium to the cortex; IMP:MGI.
DR   GO; GO:0038130; P:ERBB4 signaling pathway; IPI:MGI.
DR   GO; GO:0038138; P:ERBB4-ERBB4 signaling pathway; IPI:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR   GO; GO:0030879; P:mammary gland development; IDA:MGI.
DR   GO; GO:0060596; P:mammary placode formation; IMP:MGI.
DR   GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:MGI.
DR   GO; GO:2001223; P:negative regulation of neuron migration; IDA:MGI.
DR   GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR   GO; GO:0007416; P:synapse assembly; IDA:SynGO.
DR   Gene3D; 2.10.25.10; Laminin; 1.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR040180; Neuregulin.
DR   PANTHER; PTHR11100; HEREGULIN-NEUREGULIN FAMILY MEMBER; 1.
DR   PANTHER; PTHR11100:SF18; PRO-NEUREGULIN-3, MEMBRANE-BOUND ISOFORM; 1.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   Genevisible; O35181; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; EGF-like domain; Growth factor; Membrane;
KW   Reference proteome; Secreted; Transmembrane; Transmembrane helix.
FT   CHAIN           1..713
FT                   /note="Pro-neuregulin-3, membrane-bound isoform"
FT                   /id="PRO_0000019483"
FT   CHAIN           1..361
FT                   /note="Neuregulin-3"
FT                   /id="PRO_0000019484"
FT   TOPO_DOM        1..362
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        363..383
FT                   /note="Helical; Note=Internal signal sequence"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        384..713
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          288..331
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   REGION          28..48
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          119..220
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          251..282
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          449..496
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        121..163
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        179..208
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        251..280
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        292..306
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        300..319
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        321..330
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ   SEQUENCE   713 AA;  77370 MW;  9F7D1D5E7FC8DCF0 CRC64;
     MSEGAAGASP PGAASAAAAS AEEGTAAAAA AAAAGGGPDG GGEGAAEPPR ELRCSDCIVW
     NRQQTWLCVV PLFIGFIGLG LSLMLLKWIV VGSVKEYVPT DLVDSKGMGQ DPFFLSKPSS
     FPKAMETTTT TTSTTSPATP SAGGAASSRT PNRISTRLTT ITRAPTRFPG HRVPIRASPR
     STTARNTAAP PTVLSTTAPF FSSSTPGSRP PMPGAPSTQA MPSWPTAAYA TSSYLHDSTP
     SWTLSPFQDA AAASSSSPSS TSSTTTTPET STSPKFHTTT YSTERSEHFK PCRDKDLAYC
     LNDGECFVIE TLTGSHKHCR CKEGYQGVRC DQFLPKTDSI LSDPTDHLGI EFMESEDVYQ
     RQVLSISCII FGIVIVGMFC AAFYFKSKKQ AKQIQEHLKE SQNGKNYSLK ASSTKSESLM
     KSHVHLQNYS KADRHPVTAL EKIMESSFSA PQSFPEVTSP DRGSQPIKHH SPGQRSGMLH
     RNTFRRAPPS PRSRLGGIVG PAYQQLEESR IPDQDTIPCQ GIEVRKTISH LPIQLWCVER
     PLDLKYVSNG LRTQQNASIN MQLPSRETNP YFNSLDQKDL VGYLSPRANS VPIIPSMGLE
     ETCMQMPGIS DVKSIKWCKN SYSADIVNAS MPVSDCLLEE QQEVKILLET VQEQIRILTD
     ARRSEDFELA SMETEDSASE NTAFLPLSPT AKSEREAQFV LRNEIQRDSV LTK
//