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Database: UniProt
Entry: O35569
LinkDB: O35569
Original site: O35569 
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   16-JAN-2019, entry version 149.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 128-162, AND
RP   ALTERNATIVE SPLICING.
RX   PubMed=9348101; DOI=10.1093/oxfordjournals.jbchem.a021806;
RA   Higashiyama S., Horikawa M., Yamada K., Ichino N., Nakano N.,
RA   Nakagawa T., Miyagawa J., Matsushita N., Nagatsu T., Taniguchi N.,
RA   Ishiguro H.;
RT   "A novel brain-derived member of the epidermal growth factor family
RT   that 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
RT   gene.";
RL   Nature 387:509-512(1997).
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. May also promote the
CC       heterodimerization with the EGF receptor.
CC   -!- SUBUNIT: Interacts with ERBB3 and ERBB4.
CC   -!- SUBCELLULAR LOCATION: Pro-neuregulin-2, membrane-bound isoform:
CC       Cell 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,
CC       especially the olfactory bulb and cerebellum where it localizes in
CC       granule and Purkinje cells. In the hippocampus, found in the
CC       granule cells of the dentate gyrus. In the basal forebrain, found
CC       in the cholinergic cells. In the hindbrain, weakly detectable in
CC       the motor trigeminal nucleus. Not detected in the hypothalamus.
CC       Also found in the liver and in the thymus. Not detected in heart,
CC       adrenal gland, or testis.
CC   -!- DEVELOPMENTAL STAGE: In the embryo, expressed in the brain of
CC       E11.5 embryos where it is found in the telencephalon, but not in
CC       the hindbrain. Not found in the heart. In the adult, found in
CC       brain and thymus.
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. {ECO:0000250}.
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. {ECO:0000250}.
CC   -!- PTM: Extensive glycosylation precedes the proteolytic cleavage.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the neuregulin family. {ECO:0000305}.
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   UniGene; Rn.22434; -.
DR   ProteinModelPortal; O35569; -.
DR   SMR; O35569; -.
DR   BioGrid; 268631; 2.
DR   STRING; 10116.ENSRNOP00000025901; -.
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; ENOG410IGZW; Eukaryota.
DR   eggNOG; ENOG410Y95Z; LUCA.
DR   HOGENOM; HOG000273863; -.
DR   HOVERGEN; HBG006531; -.
DR   InParanoid; O35569; -.
DR   KO; K05456; -.
DR   OrthoDB; 313400at2759; -.
DR   PhylomeDB; O35569; -.
DR   PRO; PR:O35569; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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; IEA:UniProtKB-SubCell.
DR   GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:RGD.
DR   GO; GO:0005006; F:epidermal growth factor-activated receptor activity; IDA:RGD.
DR   GO; GO:0043125; F:ErbB-3 class receptor binding; IDA:RGD.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA: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; 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   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; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Growth factor; Immunoglobulin domain; Membrane;
KW   Reference proteome; Secreted; Transmembrane; Transmembrane helix.
FT   PROPEP        1    127       {ECO:0000269|PubMed:9348101}.
FT                                /FTId=PRO_0000019478.
FT   CHAIN       128    868       Pro-neuregulin-2, membrane-bound isoform.
FT                                /FTId=PRO_0000019479.
FT   CHAIN       128    428       Neuregulin-2.
FT                                /FTId=PRO_0000019480.
FT   TOPO_DOM    128    429       Extracellular. {ECO:0000255}.
FT   TRANSMEM    430    450       Helical; Note=Internal signal sequence.
FT                                {ECO:0000255}.
FT   TOPO_DOM    451    868       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      253    348       Ig-like C2-type.
FT   DOMAIN      357    398       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   COMPBIAS     22     32       Poly-Ser.
FT   COMPBIAS     35     45       Poly-Ser.
FT   COMPBIAS     56     59       Poly-Thr.
FT   COMPBIAS    103    106       Poly-Ala.
FT   COMPBIAS    346    356       Ser/Thr-rich.
FT   COMPBIAS    739    745       Poly-Pro.
FT   CARBOHYD     33     33       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     34     34       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    163    163       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    294    294       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    362    362       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    273    327       {ECO:0000250}.
FT   DISULFID    361    375       {ECO:0000250}.
FT   DISULFID    369    386       {ECO:0000250}.
FT   DISULFID    388    397       {ECO:0000250}.
FT   VAR_SEQ       1    108       Missing (in isoform 7).
FT                                {ECO:0000303|PubMed:9168114}.
FT                                /FTId=VSP_003465.
FT   VAR_SEQ     220    222       PLV -> FFF (in isoform 3). {ECO:0000305}.
FT                                /FTId=VSP_003466.
FT   VAR_SEQ     388    388       C -> G (in isoform 5). {ECO:0000305}.
FT                                /FTId=VSP_003467.
FT   VAR_SEQ     389    868       Missing (in isoform 5). {ECO:0000305}.
FT                                /FTId=VSP_003468.
FT   VAR_SEQ     390    421       NGFFGQRCLEKLPLRLYMPDPKQKHLGFELKE -> VGYTG
FT                                DRCQQFAMVNFSK (in isoform 4).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_003470.
FT   VAR_SEQ     390    412       NGFFGQRCLEKLPLRLYMPDPKQ -> VGYTGDRCQQFAMV
FT                                NFS (in isoform 7).
FT                                {ECO:0000303|PubMed:9168114}.
FT                                /FTId=VSP_003469.
FT   VAR_SEQ     414    439       HLGFELKEAEELYQKRVLTITGICVA -> SVLWDTPGTGV
FT                                SSSQWSTSPSTLDLN (in isoform 6).
FT                                {ECO:0000303|PubMed:9168114}.
FT                                /FTId=VSP_003472.
FT   VAR_SEQ     414    421       Missing (in isoform 2 and isoform 3).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_003471.
FT   VAR_SEQ     440    868       Missing (in isoform 6).
FT                                {ECO:0000303|PubMed:9168114}.
FT                                /FTId=VSP_003473.
FT   CONFLICT    117    117       S -> F (in Ref. 2). {ECO:0000305}.
FT   CONFLICT    724    724       R -> H (in Ref. 2). {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
//
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