NRG4_MOUSE
ID NRG4_MOUSE Reviewed; 115 AA.
AC Q9WTX4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Pro-neuregulin-4, membrane-bound isoform;
DE Short=Pro-NRG4;
DE Contains:
DE RecName: Full=Neuregulin-4;
DE Short=NRG-4;
GN Name=Nrg4;
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 STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=10348342; DOI=10.1038/sj.onc.1202631;
RA Harari D., Tzahar E., Romano J., Shelly M., Pierce J.H., Andrews G.C.,
RA Yarden Y.;
RT "Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor
RT tyrosine kinase.";
RL Oncogene 18:2681-2689(1999).
CC -!- FUNCTION: Low affinity ligand for the ERBB4 tyrosine kinase receptor.
CC Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in
CC ligand-stimulated tyrosine phosphorylation and activation of the ERBB
CC receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors.
CC {ECO:0000269|PubMed:10348342}.
CC -!- SUBUNIT: Interacts with ERBB4. {ECO:0000269|PubMed:10348342}.
CC -!- SUBCELLULAR LOCATION: [Pro-neuregulin-4, 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-4]: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=At least 3 isoforms may be produced.;
CC Name=1;
CC IsoId=Q9WTX4-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Highly expressed in pancreas; weakly expressed in
CC muscle.
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; AF083067; AAD21874.1; -; mRNA.
DR CCDS; CCDS52801.1; -. [Q9WTX4-1]
DR RefSeq; NP_114391.1; NM_032002.2. [Q9WTX4-1]
DR RefSeq; XP_017169193.1; XM_017313704.1. [Q9WTX4-1]
DR RefSeq; XP_017169194.1; XM_017313705.1. [Q9WTX4-1]
DR RefSeq; XP_017169195.1; XM_017313706.1. [Q9WTX4-1]
DR AlphaFoldDB; Q9WTX4; -.
DR SMR; Q9WTX4; -.
DR STRING; 10090.ENSMUSP00000130929; -.
DR GlyGen; Q9WTX4; 2 sites.
DR PaxDb; Q9WTX4; -.
DR PRIDE; Q9WTX4; -.
DR ProteomicsDB; 253015; -. [Q9WTX4-1]
DR Antibodypedia; 2623; 230 antibodies from 23 providers.
DR DNASU; 83961; -.
DR Ensembl; ENSMUST00000130158; ENSMUSP00000115247; ENSMUSG00000032311. [Q9WTX4-1]
DR Ensembl; ENSMUST00000164721; ENSMUSP00000130929; ENSMUSG00000032311. [Q9WTX4-1]
DR GeneID; 83961; -.
DR KEGG; mmu:83961; -.
DR UCSC; uc009psf.2; mouse. [Q9WTX4-1]
DR CTD; 145957; -.
DR MGI; MGI:1933833; Nrg4.
DR VEuPathDB; HostDB:ENSMUSG00000032311; -.
DR eggNOG; ENOG502S5EK; Eukaryota.
DR GeneTree; ENSGT00390000014815; -.
DR InParanoid; Q9WTX4; -.
DR OMA; EYWKVQS; -.
DR OrthoDB; 1521132at2759; -.
DR PhylomeDB; Q9WTX4; -.
DR BioGRID-ORCS; 83961; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Nrg4; mouse.
DR PRO; PR:Q9WTX4; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9WTX4; protein.
DR Bgee; ENSMUSG00000032311; Expressed in animal zygote and 91 other tissues.
DR ExpressionAtlas; Q9WTX4; baseline and differential.
DR Genevisible; Q9WTX4; MM.
DR GO; GO:0005615; C:extracellular space; IPI:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0048018; F:receptor ligand activity; IPI:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR GO; GO:0038138; P:ERBB4-ERBB4 signaling pathway; IPI:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IEA:InterPro.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR040180; Neuregulin.
DR PANTHER; PTHR11100; PTHR11100; 1.
DR SMART; SM00181; EGF; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; EGF-like domain;
KW Glycoprotein; Growth factor; Membrane; Reference proteome; Secreted;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..115
FT /note="Pro-neuregulin-4, membrane-bound isoform"
FT /id="PRO_0000019487"
FT CHAIN 1..61
FT /note="Neuregulin-4"
FT /id="PRO_0000019488"
FT TOPO_DOM 1..62
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical; Note=Internal signal sequence"
FT /evidence="ECO:0000255"
FT TOPO_DOM 84..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 5..46
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 9..23
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 17..34
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 36..45
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ SEQUENCE 115 AA; 12744 MW; 989A1E376F857B49 CRC64;
MPTDHEQPCG PRHRSFCLNG GICYVIPTIP SPFCRCIENY TGARCEEVFL PSSSIPSESN
LSAAFVVLAV LLTLTIAALC FLCRKGHLQR ASSVQCEISL VETNNTRTRH SHREH
