NRG2_MOUSE
ID NRG2_MOUSE Reviewed; 756 AA.
AC P56974;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Pro-neuregulin-2, membrane-bound isoform;
DE Short=Pro-NRG2;
DE Contains:
DE RecName: Full=Neuregulin-2;
DE Short=NRG-2;
DE AltName: Full=Divergent of neuregulin 1;
DE Short=DON-1;
DE Flags: Precursor;
GN Name=Nrg2;
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 (ISOFORMS DON-1S; NRG2-10 AND NRG2-16A), FUNCTION, AND
RP INTERACTION WITH ERBB3 AND ERBB4.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=9168115; DOI=10.1038/387512a0;
RA Carraway K.L. III, Weber J.L., Unger M.J., Ledesma J., Yu N., Gassmann M.,
RA Lai C.;
RT "Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases.";
RL Nature 387:512-516(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE OF 150-756 (ISOFORMS DON-1M AND DON-1S).
RC TISSUE=Choroid plexus;
RX PubMed=9199335; DOI=10.1128/mcb.17.7.4007;
RA Busfield S.J., Michnick D.A., Chickering T.W., Revett T.L., Ma J.,
RA Woolf E.A., Comrack C.A., Dussault B.J., Woolf J., Goodearl A.D.J.,
RA Gearing D.P.;
RT "Characterization of a neuregulin-related gene, Don-1, that is highly
RT expressed in restricted regions of the cerebellum and hippocampus.";
RL Mol. Cell. Biol. 17:4007-4014(1997).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. May also promote the heterodimerization with the EGF
CC receptor. {ECO:0000269|PubMed:9168115}.
CC -!- SUBUNIT: Interacts with ERBB3 and ERBB4. {ECO:0000269|PubMed:9168115}.
CC -!- SUBCELLULAR LOCATION: [Pro-neuregulin-2, 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-2]: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=NRG2-16A;
CC IsoId=P56974-1; Sequence=Displayed;
CC Name=DON-1M;
CC IsoId=P56974-2; Sequence=VSP_003464;
CC Name=DON-1S; Synonyms=NRG2-5;
CC IsoId=P56974-3; Sequence=VSP_003462, VSP_003463;
CC Name=NRG2-10;
CC IsoId=P56974-4; Sequence=VSP_003460, VSP_003461;
CC -!- TISSUE SPECIFICITY: Highest expression in the brain, with lower levels
CC in the lung. In the cerebellum, found in granule and Purkinje cells.
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 AlphaFoldDB; P56974; -.
DR SMR; P56974; -.
DR STRING; 10090.ENSMUSP00000111378; -.
DR GlyConnect; 2613; 1 N-Linked glycan (1 site).
DR GlyGen; P56974; 4 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P56974; -.
DR PhosphoSitePlus; P56974; -.
DR PaxDb; P56974; -.
DR PRIDE; P56974; -.
DR ProteomicsDB; 252852; -. [P56974-1]
DR ProteomicsDB; 252853; -. [P56974-2]
DR ProteomicsDB; 252854; -. [P56974-3]
DR ProteomicsDB; 252855; -. [P56974-4]
DR MGI; MGI:1098246; Nrg2.
DR eggNOG; ENOG502QRNM; Eukaryota.
DR InParanoid; P56974; -.
DR ChiTaRS; Nrg2; mouse.
DR PRO; PR:P56974; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P56974; protein.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO: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:0005006; F:epidermal growth factor receptor activity; ISO:MGI.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; ISO:MGI.
DR GO; GO:1990631; F:ErbB-4 class receptor binding; ISO:MGI.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:MGI.
DR GO; GO:0048018; F:receptor ligand activity; IDA: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:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; IDA:MGI.
DR GO; GO:0038130; P:ERBB4 signaling pathway; IDA:MGI.
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:0007399; P:nervous system development; IEA:InterPro.
DR GO; GO:0051963; P:regulation of synapse assembly; ISO:MGI.
DR GO; GO:0090128; P:regulation of synapse maturation; ISO:MGI.
DR Gene3D; 2.60.40.10; -; 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 PANTHER; PTHR11100; PTHR11100; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF02158; Neuregulin; 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 Alternative splicing; Cell membrane; Disulfide bond; EGF-like domain;
KW Glycoprotein; Growth factor; Immunoglobulin domain; Membrane;
KW Reference proteome; Secreted; Transmembrane; Transmembrane helix.
FT PROPEP 1..19
FT /evidence="ECO:0000250"
FT /id="PRO_0000019475"
FT CHAIN 20..756
FT /note="Pro-neuregulin-2, membrane-bound isoform"
FT /id="PRO_0000019476"
FT CHAIN 20..314
FT /note="Neuregulin-2"
FT /id="PRO_0000019477"
FT TOPO_DOM 20..315
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 316..336
FT /note="Helical; Note=Internal signal sequence"
FT /evidence="ECO:0000255"
FT TOPO_DOM 337..756
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 145..240
FT /note="Ig-like C2-type"
FT DOMAIN 249..290
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 402..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 557..578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 608..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 711..756
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..426
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 666..680
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 727..744
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 165..219
FT /evidence="ECO:0000250"
FT DISULFID 253..267
FT /evidence="ECO:0000250"
FT DISULFID 261..278
FT /evidence="ECO:0000250"
FT DISULFID 280..289
FT /evidence="ECO:0000250"
FT VAR_SEQ 280
FT /note="C -> G (in isoform NRG2-10)"
FT /evidence="ECO:0000305"
FT /id="VSP_003460"
FT VAR_SEQ 281..756
FT /note="Missing (in isoform NRG2-10)"
FT /evidence="ECO:0000305"
FT /id="VSP_003461"
FT VAR_SEQ 282..330
FT /note="VGYTGDRCQQFAMVNFSKHLGFELKEAEELYQKRVLTITGICVALLVVG ->
FT NGFFGQRCLEKLPLRLYMPDPKQSVLWDTPGTGVSSSQWSTSPSTLDLN (in
FT isoform DON-1S)"
FT /evidence="ECO:0000305"
FT /id="VSP_003462"
FT VAR_SEQ 282..307
FT /note="VGYTGDRCQQFAMVNFSKHLGFELKE -> NGFFGQRCLEKLPLRLYMPDPK
FT QK (in isoform DON-1M)"
FT /evidence="ECO:0000305"
FT /id="VSP_003464"
FT VAR_SEQ 331..756
FT /note="Missing (in isoform DON-1S)"
FT /evidence="ECO:0000305"
FT /id="VSP_003463"
SQ SEQUENCE 756 AA; 82213 MW; 51D85DC918BE678E CRC64;
MRRDPAPGFS MLLFGVSLAC YSPSLKSVQD QAYKAPVVVE GKVQGLAPAG GSSSNSTREP
PASGRVALVK VLDKWPLRSG GLQREQVISV GSCAPLERNQ RYIFFLEPTE QPLVFKTAFA
PVDPNGKNIK KEVGKILCTD CATRPKLKKM KSQTGEVGEK QSLKCEAAAG NPQPSYRWFK
DGKELNRSRD IRIKYGNGRK NSRLQFNKVR VEDAGEYVCE AENILGKDTV RGRLHVNSVS
TTLSSWSGHA RKCNETAKSY CVNGGVCYYI EGINQLSCKC PVGYTGDRCQ QFAMVNFSKH
LGFELKEAEE LYQKRVLTIT GICVALLVVG IVCVVAYCKT KKQRRQMHHH LRQNMCPAHQ
NRSLANGPSH PRLDPEEIQM ADYISKNVPA TDHVIRREAE TTFSGSHSCS PSHHCSTATP
TSSHRHESHT WSLERSESLT SDSQSGIMLS SVGTSKCNSP ACVEARARRA AAYSQEERRR
AAMPPYHDSI DSLRDSPHSE RYVSALTTPA RLSPVDFHYS LATQVPTFEI TSPNSAHAVS
LPPAAPISYR LAEQQPLLRH PAPPGPGPGS GPGADMQRSY DSYYYPAAGP GPRRSACALG
GSLGSLPASP FRIPEDDEYE TTQECAPPPP PRPRTRGASR RTSAGPRRWR RSRLNGLAAQ
RARAARDSLS LSSGSGCGSA SASDDDADDA DGALAAESTP FLGLRAAHDA LRSDSPPLCP
AADSRTYYSL DSHSTRASSR HSRGPPTRAK QDSGPL
