NRG1_XENLA
ID NRG1_XENLA Reviewed; 677 AA.
AC O93383; Q9W6N0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 25-MAY-2022, entry version 117.
DE RecName: Full=Pro-neuregulin-1, membrane-bound isoform;
DE Short=Pro-NRG1;
DE Contains:
DE RecName: Full=Neuregulin-1;
DE Flags: Precursor;
GN Name=nrg1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA1), AND ALTERNATIVE SPLICING.
RX PubMed=9685585; DOI=10.1016/s0169-328x(98)00085-0;
RA Yang J.F., Zhou H., Pun S., Ip N.Y., Peng H.B., Tsim K.W.K.;
RT "Cloning of cDNAs encoding Xenopus neuregulin: expression in myotomal
RT muscle during embryo development.";
RL Brain Res. Mol. Brain Res. 58:59-73(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRD).
RX PubMed=10383827; DOI=10.1006/mcne.1999.0759;
RA Yang J.F., Zhou H., Choi R.C., Ip N.Y., Peng H.B., Tsim K.W.K.;
RT "A cysteine-rich form of Xenopus neuregulin induces the expression of
RT acetylcholine receptors in cultured myotubes.";
RL Mol. Cell. Neurosci. 13:415-429(1999).
CC -!- FUNCTION: Direct ligand for the ERBB tyrosine kinase receptors. Induces
CC expression of acetylcholine receptor in synaptic nuclei.
CC -!- SUBCELLULAR LOCATION: [Pro-neuregulin-1, 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-1]: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist. Isoforms have alpha- or
CC beta-type EGF-like domains.;
CC Name=Alpha1;
CC IsoId=O93383-1; Sequence=Displayed;
CC Name=CRD; Synonyms=CRD-NRG1, Cysteine-rich domain;
CC IsoId=O93383-2; Sequence=VSP_003449, VSP_003450;
CC -!- TISSUE SPECIFICITY: Isoform alpha1 is expressed in brain and muscle.
CC Isoform CRD is expressed in brain and spinal cord, but at very low
CC level in muscle.
CC -!- DEVELOPMENTAL STAGE: Strong expression in developing brain and spinal
CC cord of the embryo. Also expressed in the myotomal 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.
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 -!- 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; AF076618; AAC26804.1; -; mRNA.
DR EMBL; AF142632; AAD33893.1; -; mRNA.
DR RefSeq; NP_001079063.1; NM_001085594.1. [O93383-2]
DR AlphaFoldDB; O93383; -.
DR SMR; O93383; -.
DR GeneID; 373595; -.
DR CTD; 373595; -.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0007399; P:nervous system development; IEA:InterPro.
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 InterPro; IPR018250; NRG1.
DR PANTHER; PTHR11100; PTHR11100; 1.
DR PANTHER; PTHR11100:SF25; PTHR11100:SF25; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF02158; Neuregulin; 1.
DR PRINTS; PR01089; NEUREGULIN.
DR SMART; SM00181; EGF; 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 2: Evidence at transcript 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 CHAIN 1..677
FT /note="Pro-neuregulin-1, membrane-bound isoform"
FT /evidence="ECO:0000250"
FT /id="PRO_0000019470"
FT CHAIN 1..259
FT /note="Neuregulin-1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000019471"
FT TOPO_DOM 1..260
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..280
FT /note="Helical; Note=Internal signal sequence"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..677
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 37..132
FT /note="Ig-like C2-type"
FT DOMAIN 188..232
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 350..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 457..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..100
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 296..319
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 351..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 503..519
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 583..597
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 57..116
FT /evidence="ECO:0000250"
FT DISULFID 192..206
FT /evidence="ECO:0000250"
FT DISULFID 200..220
FT /evidence="ECO:0000250"
FT DISULFID 222..231
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..136
FT /note="MAEKKKVKEGKGRKGKGKKDRKGKKAEGSDQGAAASPKLKEIKTQSVQEGKK
FT LVLKCQAVSEQPSLKFRWFKGEKEIGAKNKPDSKPEHIKIRGKKKSSELQISKASSADN
FT GEYKCMVSNQLGNDTVTVNVTIVPK -> MSEDTAEGLQNQCSEQSSDPPSAELQNEES
FT MPETQDEEETTHGITGLAITCCVCLEADRLRICLNSEKICIIPILACLISLCLCIAGLK
FT WVFVDKIFEYDSPTHLDPGHRGQDLILYTDTAPSTLVPSSVRTLPVIIPTTDSKAAVTF
FT KFGTSLLPTE (in isoform CRD)"
FT /evidence="ECO:0000303|PubMed:10383827"
FT /id="VSP_003449"
FT VAR_SEQ 223..252
FT /note="KPGFTGARCTETDPLRVVRSEKHLGIEFME -> PNEFTGDRCQNYVMASFY
FT K (in isoform CRD)"
FT /evidence="ECO:0000303|PubMed:10383827"
FT /id="VSP_003450"
SQ SEQUENCE 677 AA; 75795 MW; 49279E8F5BAE396F CRC64;
MAEKKKVKEG KGRKGKGKKD RKGKKAEGSD QGAAASPKLK EIKTQSVQEG KKLVLKCQAV
SEQPSLKFRW FKGEKEIGAK NKPDSKPEHI KIRGKKKSSE LQISKASSAD NGEYKCMVSN
QLGNDTVTVN VTIVPKPTYN HLLLMKIYLK VTSVEKSVEP STLNLLESQK EVIFATTKRG
DTTAGPGHLI KCSDKEKTYC VNGGECYVLN GITSSNQFMC KCKPGFTGAR CTETDPLRVV
RSEKHLGIEF MEAEELYQKR VLTITGICID LLVVGDMCVV DAYCKTKKQR KKLNDRLRQS
LRERNKNITN KDNRPHNPKN PPPRKNVQLV NQYVSKNVIS SEHVIERETE TSFSTSHYTS
TTHHSTTVTQ TPSHSWSNGL SESMISEKSY SVIVTSSVEN SRHTSPTGPR GRLNGIGGPR
DCSYLRHARD TPDSYRDSPH SERYVSAMTT PARMSPVEFK TPISPKSPCL ETSPPESSLA
VSVPSVAVSP FIEEERPLLL VSPPRLREKR YDRKTPQKTP HKQHNSYHHN PGHDSSSLPP
NPLRIVEDEE YETTQEYEPS LEPAKKLVNS RRQKRTKPNG HISNRLELDS DSSSESSTSE
SETEDERIGE ETPFLSIQNP LAASLESASL YRHADSRTNP TSRFSTQEEL QARLSSIANQ
ALCDQKKRKM TCKTLFI
