NRG2_RAT
ID NRG2_RAT Reviewed; 868 AA.
AC O35569; O35073; O35570; O35571; O35572;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 162.
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=Neural- and thymus-derived activator for ERBB kinases;
DE Short=NTAK;
DE Flags: Precursor;
GN Name=Nrg2; Synonyms=Ntak;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 128-162, AND ALTERNATIVE
RP SPLICING.
RX PubMed=9348101; DOI=10.1093/oxfordjournals.jbchem.a021806;
RA Higashiyama S., Horikawa M., Yamada K., Ichino N., Nakano N., Nakagawa T.,
RA Miyagawa J., Matsushita N., Nagatsu T., Taniguchi N., Ishiguro H.;
RT "A novel brain-derived member of the epidermal growth factor family that
RT interacts with ErbB3 and ErbB4.";
RL J. Biochem. 122:675-680(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 109-868 (ISOFORMS 6 AND 7).
RC TISSUE=Cerebellum;
RX PubMed=9168114; DOI=10.1038/387509a0;
RA Chang H., Riese D.J. II, Gilbert W., Stern D.F., McMahan U.J.;
RT "Ligands for ErbB-family receptors encoded by a neuregulin-like gene.";
RL Nature 387:509-512(1997).
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.
CC -!- SUBUNIT: Interacts with ERBB3 and ERBB4.
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=7;
CC Comment=Additional isoforms seem to exist. The alpha-type and
CC beta-type differ in the EGF-like domain.;
CC Name=1; Synonyms=NTAK-alpha1;
CC IsoId=O35569-1; Sequence=Displayed;
CC Name=2; Synonyms=NTAK-alpha2A;
CC IsoId=O35569-2; Sequence=VSP_003471;
CC Name=3; Synonyms=NTAK-alpha2B, NTAK-alpha2-1P;
CC IsoId=O35569-3; Sequence=VSP_003466, VSP_003471;
CC Name=4; Synonyms=NTAK-beta;
CC IsoId=O35569-4; Sequence=VSP_003470;
CC Name=5; Synonyms=NTAK-gamma;
CC IsoId=O35569-5; Sequence=VSP_003467, VSP_003468;
CC Name=6; Synonyms=NRG2-alpha;
CC IsoId=O35569-6; Sequence=VSP_003472, VSP_003473;
CC Name=7; Synonyms=NRG2-beta;
CC IsoId=O35569-7; Sequence=VSP_003465, VSP_003469;
CC -!- TISSUE SPECIFICITY: Expressed in most parts of the brain, especially
CC the olfactory bulb and cerebellum where it localizes in granule and
CC Purkinje cells. In the hippocampus, found in the granule cells of the
CC dentate gyrus. In the basal forebrain, found in the cholinergic cells.
CC In the hindbrain, weakly detectable in the motor trigeminal nucleus.
CC Not detected in the hypothalamus. Also found in the liver and in the
CC thymus. Not detected in heart, adrenal gland, or testis.
CC -!- DEVELOPMENTAL STAGE: In the embryo, expressed in the brain of E11.5
CC embryos where it is found in the telencephalon, but not in the
CC hindbrain. Not found in the heart. In the adult, found in brain and
CC thymus.
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}.
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; D89995; BAA23344.1; -; mRNA.
DR EMBL; D89996; BAA23345.1; -; mRNA.
DR EMBL; D89997; BAA23346.1; -; mRNA.
DR EMBL; D89998; BAA23347.1; -; mRNA.
DR EMBL; AB001576; BAA23348.1; -; mRNA.
DR PIR; JC5701; JC5701.
DR PIR; JC5702; JC5702.
DR RefSeq; NP_001129623.1; NM_001136151.1. [O35569-2]
DR AlphaFoldDB; O35569; -.
DR SMR; O35569; -.
DR BioGRID; 268631; 2.
DR STRING; 10116.ENSRNOP00000025901; -.
DR GlyGen; O35569; 5 sites.
DR PhosphoSitePlus; O35569; -.
DR PaxDb; O35569; -.
DR PRIDE; O35569; -.
DR GeneID; 432361; -.
DR KEGG; rno:432361; -.
DR UCSC; RGD:1303302; rat. [O35569-1]
DR CTD; 9542; -.
DR RGD; 1303302; Nrg2.
DR eggNOG; ENOG502QRNM; Eukaryota.
DR InParanoid; O35569; -.
DR OrthoDB; 313400at2759; -.
DR PhylomeDB; O35569; -.
DR PRO; PR:O35569; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0098839; C:postsynaptic density membrane; ISO:RGD.
DR GO; GO:0005006; F:epidermal growth factor receptor activity; IDA:RGD.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:RGD.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; IDA:RGD.
DR GO; GO:1990631; F:ErbB-4 class receptor binding; IDA:MGI.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:RGD.
DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; ISO:RGD.
DR GO; GO:0038130; P:ERBB4 signaling pathway; IDA:MGI.
DR GO; GO:0038138; P:ERBB4-ERBB4 signaling pathway; ISO:RGD.
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; IDA:SynGO.
DR GO; GO:0090128; P:regulation of synapse maturation; IDA:SynGO.
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; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Growth factor;
KW Immunoglobulin domain; Membrane; Reference proteome; Secreted;
KW Transmembrane; Transmembrane helix.
FT PROPEP 1..127
FT /evidence="ECO:0000269|PubMed:9348101"
FT /id="PRO_0000019478"
FT CHAIN 128..868
FT /note="Pro-neuregulin-2, membrane-bound isoform"
FT /id="PRO_0000019479"
FT CHAIN 128..428
FT /note="Neuregulin-2"
FT /id="PRO_0000019480"
FT TOPO_DOM 128..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..450
FT /note="Helical; Note=Internal signal sequence"
FT /evidence="ECO:0000255"
FT TOPO_DOM 451..868
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 253..348
FT /note="Ig-like C2-type"
FT DOMAIN 357..398
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 1..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 469..488
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 516..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..690
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 720..806
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 823..868
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 19..72
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..90
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 778..792
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..856
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 273..327
FT /evidence="ECO:0000250"
FT DISULFID 361..375
FT /evidence="ECO:0000250"
FT DISULFID 369..386
FT /evidence="ECO:0000250"
FT DISULFID 388..397
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..108
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:9168114"
FT /id="VSP_003465"
FT VAR_SEQ 220..222
FT /note="PLV -> FFF (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_003466"
FT VAR_SEQ 388
FT /note="C -> G (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_003467"
FT VAR_SEQ 389..868
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_003468"
FT VAR_SEQ 390..421
FT /note="NGFFGQRCLEKLPLRLYMPDPKQKHLGFELKE -> VGYTGDRCQQFAMVNF
FT SK (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_003470"
FT VAR_SEQ 390..412
FT /note="NGFFGQRCLEKLPLRLYMPDPKQ -> VGYTGDRCQQFAMVNFS (in
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:9168114"
FT /id="VSP_003469"
FT VAR_SEQ 414..439
FT /note="HLGFELKEAEELYQKRVLTITGICVA -> SVLWDTPGTGVSSSQWSTSPST
FT LDLN (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:9168114"
FT /id="VSP_003472"
FT VAR_SEQ 414..421
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_003471"
FT VAR_SEQ 440..868
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:9168114"
FT /id="VSP_003473"
FT CONFLICT 117
FT /note="S -> F (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 724
FT /note="R -> H (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 868 AA; 93777 MW; 3C7D4D94DBE64DE2 CRC64;
MRQVCCSALP PPLEKARCSS YSYSDSSSSS SSNNSSSSTS SRSSSRSSSR SSRGSTTTTS
SSENSGSNSG SIFRPAAPPE PRPQPQPQPR SPAARRAAAR SRAAAAGGMR RDPAPGSSML
LFGVSLACYS PSLKSVQDQA YKAPVVVEGK VQGLAPAGGS SSNSTREPPA SGRVALVKVL
DKWPLRSGGL QREQVISVGS CAPLERNQRY IFFLEPTEQP LVFKTAFAPV DPNGKNIKKE
VGKILCTDCA TRPKLKKMKS QTGEVGEKQS LKCEAAAGNP QPSYRWFKDG KELNRSRDIR
IKYGNGRKNS RLQFNKVKVE DAGEYVCEAE NILGKDTVRG RLHVNSVSTT LSSWSGHARK
CNETAKSYCV NGGVCYYIEG INQLSCKCPN GFFGQRCLEK LPLRLYMPDP KQKHLGFELK
EAEELYQKRV LTITGICVAL LVVGIVCVVA YCKTKKQRRQ MHHHLRQNMC PAHQNRSLAN
GPSHPRLDPE EIQMADYISK NVPATDHVIR REAETTFSGS HSCSPSHHCS TATPTSSHRH
ESHTWSLERS ESLTSDSQSG IMLSSVGTSK CNSPACVEAR ARRAAAYSQE ERRRAAMPPY
HDSIDSLRDS PHSERYVSAL TTPARLSPVD FHYSLATQVP TFEITSPNSA HAVSLPPAAP
ISYRLAEQQP LLRHPAPPGP GPGPGADMQR SYDSYYYPAA GPGPRRGACA LGGSLGSLPA
SPFRIPEDDE YETTQECAPP PPPRPRTRGA SRRTSAGPRR WRRSRLNGLA AQRARAARDS
LSLSSGSGCG SASASDDDAD DADGALAAES TPFLGLRAAH DALRSDSPPL CPAADSRTYY
SLDSHSTRAS SRHSRGPPTR AKQDSGPL
