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Q05199

- NRG1_CHICK

UniProt

Q05199 - NRG1_CHICK

Protein

Pro-neuregulin-1, membrane-bound isoform

Gene

NRG1

Organism
Gallus gallus (Chicken)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Direct ligand for the ERBB tyrosine kinase receptors. The multiple isoforms perform diverse functions: cysteine-rich domain containing isoforms (isoform 2-isoform 4) probably regulate the expression of nicotinic acetylcholine receptors at developing interneuronal synapses. Isoform Ig-NRG is required for the initial induction and/or maintenance of the mature levels of acetylcholine receptors at neuromuscular synapses.

    GO - Biological processi

    1. embryo development Source: InterPro

    Keywords - Molecular functioni

    Growth factor

    Enzyme and pathway databases

    ReactomeiREACT_189763. Signaling by ERBB2.
    REACT_194392. GRB2 events in ERBB2 signaling.
    REACT_194393. SHC1 events in ERBB4 signaling.
    REACT_194394. Signaling by ERBB4.
    REACT_194410. SHC1 events in ERBB2 signaling.
    REACT_196847. PI3K events in ERBB4 signaling.
    REACT_196849. PI3K events in ERBB2 signaling.
    REACT_197054. Nuclear signaling by ERBB4.
    REACT_198076. Constitutive PI3K/AKT Signaling in Cancer.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pro-neuregulin-1, membrane-bound isoform
    Short name:
    Pro-NRG1
    Cleaved into the following chain:
    Alternative name(s):
    Acetylcholine receptor-inducing activity
    Short name:
    ARIA
    Gene namesi
    Name:NRG1
    Synonyms:ARIA
    OrganismiGallus gallus (Chicken)
    Taxonomic identifieri9031 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus
    ProteomesiUP000000539: Chromosome Z

    Subcellular locationi

    Chain Pro-neuregulin-1, membrane-bound isoform : Cell membrane By similarity; Single-pass type I membrane protein By similarity
    Note: Does not seem to be active.By similarity

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 602602Pro-neuregulin-1, membrane-bound isoformPRO_0000019468Add
    BLAST
    Chaini1 – 205205Neuregulin-1PRO_0000019469Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi21 – 211N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi49 ↔ 105By similarity
    Glycosylationi113 – 1131N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi141 ↔ 155By similarity
    Disulfide bondi149 ↔ 169By similarity
    Disulfide bondi171 ↔ 180By similarity

    Post-translational modificationi

    Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.
    Extensive glycosylation precedes the proteolytic cleavage.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ05199.
    PRIDEiQ05199.

    Expressioni

    Developmental stagei

    Isoform 2-isoform 4 are detected at embryonic day 4 (ED4) in both visceral and somatic motor neurons of spinal cord and is highest at ED6. Isoform 1 is not expressed until ED 6 in spinal cord. At ED 11 both isoforms display comparable levels.

    Structurei

    3D structure databases

    ProteinModelPortaliQ05199.
    SMRiQ05199. Positions 136-203.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 206206ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini230 – 602373CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei207 – 22923Helical; Note=Internal signal sequenceSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini29 – 12395Ig-like C2-typeAdd
    BLAST
    Domaini137 – 18145EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi125 – 13612Ser/Thr-richAdd
    BLAST

    Domaini

    The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization By similarity.By similarity
    ERBB receptor binding is elicited entirely by the EGF-like domain.

    Sequence similaritiesi

    Belongs to the neuregulin family.Curated
    Contains 1 EGF-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Immunoglobulin domain, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG47801.
    GeneTreeiENSGT00710000106660.
    HOGENOMiHOG000273863.
    HOVERGENiHBG006531.
    KOiK05455.
    PhylomeDBiQ05199.

    Family and domain databases

    Gene3Di2.60.40.10. 1 hit.
    InterProiIPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR013098. Ig_I-set.
    IPR003598. Ig_sub2.
    IPR018250. Neuregulin.
    IPR002154. Neuregulin_1_C.
    [Graphical view]
    PfamiPF07679. I-set. 1 hit.
    PF02158. Neuregulin. 1 hit.
    [Graphical view]
    PRINTSiPR01089. NEUREGULIN.
    SMARTiSM00181. EGF. 1 hit.
    SM00408. IGc2. 1 hit.
    [Graphical view]
    PROSITEiPS00022. EGF_1. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS50835. IG_LIKE. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: Q05199-1) [UniParc]FASTAAdd to Basket

    Also known as: ARIA, Ig-NRG

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MWATSEGPLQ YSLAPTQTDV NSSYNTVPPK LKEMKNQEVA VGQKLVLRCE    50
    TTSEYPALRF KWLKNGKEIT KKNRPENVKI PKKQKKYSEL HIYRATLADA 100
    GEYACRVSSK LGNDSTKASV IITDTNATST STTGTSHLTK CDIKQKAFCV 150
    NGGECYMVKD LPNPPRYLCR CPNEFTGDRC QNYVMASFYK HLGIEFMEAE 200
    ELYQKRVLTI TGICIALLVV GIMCVVAYCK TKKQRKKLHD RLRQSLRSER 250
    NNVMNMANGP HHPNPPPDNV QLVNQYVSKN IISSERVVER ETETSFSTSH 300
    YTSTTHHSMT VTQTPSHSWS NGHTESILSE SHSVLVSSSV ENSRHTSPTG 350
    PRGRLNGIGG PREGNSFLRH ARETPDSYRD SPHSERYVSA MTTPARMSPV 400
    DFHTPTSPKS PPSEMSPPVS SLTISIPSVA VSPFMDEERP LLLVTPPRLR 450
    EKYDNHLQQF NSFHNNPTHE SNSLPPSPLR IVEDEEYETT QEYEPAQEPP 500
    KKLTNSRRVK RTKPNGHISS RVEVDSDTSS QSTSSESETE DERIGEDTPF 550
    LSIQNPMATS LEPAAAYRLA ENRTNPANRF STPEELQARL SSVIANQDPI 600
    AV 602

    Note: Contains an Ig-like domain.

    Length:602
    Mass (Da):67,454
    Last modified:November 1, 1996 - v1
    Checksum:i4183C0E56CE5D346
    GO
    Isoform 2 (identifier: Q05199-2) [UniParc]FASTAAdd to Basket

    Also known as: CRD-NRG-BETA1A

    The sequence of this isoform differs from the canonical sequence as follows:
         1-127: MWATSEGPLQ...ASVIITDTNA → MSEVGTETFP...TNLQTAPKLS

    Note: The EGF-like domain is replaced by a cysteine-rich domain (CRD).

    Show »
    Length:685
    Mass (Da):75,415
    Checksum:iB2634881D40B3398
    GO
    Isoform 3 (identifier: Q05199-3) [UniParc]FASTAAdd to Basket

    Also known as: CRD-NRG-BETA2A

    The sequence of this isoform differs from the canonical sequence as follows:
         1-127: MWATSEGPLQ...ASVIITDTNA → MSEVGTETFP...TNLQTAPKLS
         191-198: Missing.

    Note: The EGF-like domain is replaced by a cysteine-rich domain (CRD).

    Show »
    Length:677
    Mass (Da):74,457
    Checksum:iD6C0F3C45B64E0EC
    GO
    Isoform 4 (identifier: Q05199-4) [UniParc]FASTAAdd to Basket

    Also known as: CRD-NRG-BETA2B

    The sequence of this isoform differs from the canonical sequence as follows:
         1-127: MWATSEGPLQ...ASVIITDTNA → MSEVGTETFP...TNLQTAPKLS
         191-198: Missing.
         388-405: VSAMTTPARMSPVDFHTP → HTPPTSLLLAGKVSLRVS
         406-602: Missing.

    Note: The EGF-like domain is replaced by a cysteine-rich domain (CRD).

    Show »
    Length:480
    Mass (Da):52,440
    Checksum:i9B95A898A4669A93
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 127127MWATS…TDTNA → MSEVGTETFPSPSAQLSPDA SLGGLPAEENMPGPHREDSR VPGVAGLASTCCVCLEAERL KGCLNSEKICIAPILACLLS LCLCIAGLKWVFVDKIFEYD SPTHLDPGRIGQDPRSTVDP TALSAWVPSEVYASPFPIPS LESKAEVTVQTDSSLVPSRP FLQPSLYNRILDVGLWSSAT PSLSPSSLEPTTASQAQATE TNLQTAPKLS in isoform 2, isoform 3 and isoform 4. 1 PublicationVSP_003445Add
    BLAST
    Alternative sequencei191 – 1988Missing in isoform 3 and isoform 4. 1 PublicationVSP_003446
    Alternative sequencei388 – 40518VSAMT…DFHTP → HTPPTSLLLAGKVSLRVS in isoform 4. 1 PublicationVSP_003447Add
    BLAST
    Alternative sequencei406 – 602197Missing in isoform 4. 1 PublicationVSP_003448Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L11264 mRNA. Translation: AAA49037.1.
    AF045654 mRNA. Translation: AAC05670.1.
    AF045655 mRNA. Translation: AAC05671.1.
    AF045656 mRNA. Translation: AAC05672.1.
    PIRiA45769.
    RefSeqiNP_989448.1. NM_204117.1. [Q05199-2]
    UniGeneiGga.135.

    Genome annotation databases

    EnsembliENSGALT00000037781; ENSGALP00000036986; ENSGALG00000015422. [Q05199-1]
    GeneIDi373906.
    KEGGigga:373906.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L11264 mRNA. Translation: AAA49037.1 .
    AF045654 mRNA. Translation: AAC05670.1 .
    AF045655 mRNA. Translation: AAC05671.1 .
    AF045656 mRNA. Translation: AAC05672.1 .
    PIRi A45769.
    RefSeqi NP_989448.1. NM_204117.1. [Q05199-2 ]
    UniGenei Gga.135.

    3D structure databases

    ProteinModelPortali Q05199.
    SMRi Q05199. Positions 136-203.
    ModBasei Search...
    MobiDBi Search...

    Proteomic databases

    PaxDbi Q05199.
    PRIDEi Q05199.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSGALT00000037781 ; ENSGALP00000036986 ; ENSGALG00000015422 . [Q05199-1 ]
    GeneIDi 373906.
    KEGGi gga:373906.

    Organism-specific databases

    CTDi 3084.

    Phylogenomic databases

    eggNOGi NOG47801.
    GeneTreei ENSGT00710000106660.
    HOGENOMi HOG000273863.
    HOVERGENi HBG006531.
    KOi K05455.
    PhylomeDBi Q05199.

    Enzyme and pathway databases

    Reactomei REACT_189763. Signaling by ERBB2.
    REACT_194392. GRB2 events in ERBB2 signaling.
    REACT_194393. SHC1 events in ERBB4 signaling.
    REACT_194394. Signaling by ERBB4.
    REACT_194410. SHC1 events in ERBB2 signaling.
    REACT_196847. PI3K events in ERBB4 signaling.
    REACT_196849. PI3K events in ERBB2 signaling.
    REACT_197054. Nuclear signaling by ERBB4.
    REACT_198076. Constitutive PI3K/AKT Signaling in Cancer.

    Miscellaneous databases

    NextBioi 20813438.
    PROi Q05199.

    Family and domain databases

    Gene3Di 2.60.40.10. 1 hit.
    InterProi IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR007110. Ig-like_dom.
    IPR013783. Ig-like_fold.
    IPR013098. Ig_I-set.
    IPR003598. Ig_sub2.
    IPR018250. Neuregulin.
    IPR002154. Neuregulin_1_C.
    [Graphical view ]
    Pfami PF07679. I-set. 1 hit.
    PF02158. Neuregulin. 1 hit.
    [Graphical view ]
    PRINTSi PR01089. NEUREGULIN.
    SMARTi SM00181. EGF. 1 hit.
    SM00408. IGc2. 1 hit.
    [Graphical view ]
    PROSITEi PS00022. EGF_1. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS50835. IG_LIKE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family."
      Falls D.L., Rosen K.M., Corfas G., Lane W.S., Fischbach G.D.
      Cell 72:801-815(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
      Strain: White leghorn.
      Tissue: Brain.
    2. "A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogenesis."
      Yang X., Kuo Y., Devay P., Yu C., Role L.
      Neuron 20:255-270(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
      Tissue: Brain and Spinal cord.

    Entry informationi

    Entry nameiNRG1_CHICK
    AccessioniPrimary (citable) accession number: Q05199
    Secondary accession number(s): O73750, O73751, O73752
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 109 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3