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P43322

- NRG1_RAT

UniProt

P43322 - NRG1_RAT

Protein

Pro-neuregulin-1, membrane-bound isoform

Gene

Nrg1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vessicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart By similarity.By similarity

    GO - Molecular functioni

    1. ErbB-3 class receptor binding Source: RGD

    GO - Biological processi

    1. embryo development Source: InterPro
    2. glucose transport Source: RGD
    3. myelination Source: RGD
    4. regulation of blood pressure Source: RGD

    Keywords - Molecular functioni

    Growth factor

    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
    Glial growth factor
    Heregulin
    Short name:
    HRG
    Neu differentiation factor
    Sensory and motor neuron-derived factor
    Gene namesi
    Name:Nrg1
    Synonyms:Ndf
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi621341. Nrg1.

    Subcellular locationi

    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
    Propeptidei1 – 13131 PublicationPRO_0000019465Add
    BLAST
    Chaini14 – 662649Pro-neuregulin-1, membrane-bound isoformPRO_0000019466Add
    BLAST
    Chaini14 – 264251Neuregulin-1PRO_0000019467Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi57 ↔ 112
    Glycosylationi120 – 1201N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi182 ↔ 196By similarity
    Disulfide bondi190 ↔ 210By similarity
    Disulfide bondi212 ↔ 221By 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.
    N- and O-glycosylated By similarity. Extensive glycosylation precedes the proteolytic cleavage.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP43322.
    PRIDEiP43322.

    PTM databases

    PhosphoSiteiP43322.

    Expressioni

    Tissue specificityi

    Widely expressed. Most tissues contain isoform alpha2A and isoform alpha2B. Isoform Alpha2 and isoform beta2 are the predominant forms in mesenchymal and non-neuronal organs. Isoform Beta1 is enriched in brain and spinal cord, but not in muscle and heart. Isoform Alpha2C is highly expressed in spinal cord, moderately in lung, brain, ovary, and stomach, in low amounts in the kidney, skin and heart and not detected in the liver, spleen, and placenta.

    Gene expression databases

    GenevestigatoriP43322.

    Interactioni

    Subunit structurei

    The cytoplasmic domain interacts with the LIM domain region of LIMK1. Interacts with ERBB3 and ERBB4.1 Publication

    Protein-protein interaction databases

    MINTiMINT-4996739.

    Structurei

    3D structure databases

    ProteinModelPortaliP43322.
    SMRiP43322. Positions 177-225.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini14 – 265252ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini289 – 662374CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei266 – 28823Helical; Note=Internal signal sequenceSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini37 – 12892Ig-like C2-typeAdd
    BLAST
    Domaini178 – 22245EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi165 – 17713Ser/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.
    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.
    HOVERGENiHBG006531.
    KOiK05455.
    PhylomeDBiP43322.

    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 (8)i

    Sequence statusi: Complete.

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

    This entry describes 8 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform Beta4 (identifier: P43322-1) [UniParc]FASTAAdd to Basket

    Also known as: NDF42A

    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

    MSERKEGRGK GKGKKKDRGS RGKPGPAEGD PSPALPPRLK EMKSQESAAG    50
    SKLVLRCETS SEYSSLRFKW FKNGNELNRK NKPENIKIQK KPGKSELRIN 100
    KASLADSGEY MCKVISKLGN DSASANITIV ESNEFITGMP ASTETAYVSS 150
    ESPIRISVST EGANTSSSTS TSTTGTSHLI KCAEKEKTFC VNGGECFTVK 200
    DLSNPSRYLC KCPNEFTGDR CQNYVMASFY MTSRRKRQET EKPLERKLDH 250
    SLVKESKAEE LYQKRVLTIT GICIALLVVG IMCVVAYCKT KKQRQKLHDR 300
    LRQSLRSERS NLVNIANGPH HPNPPPENVQ LVNQYVSKNV ISSEHIVERE 350
    VETSFSTSHY TSTAHHSTTV TQTPSHSWSN GHTESVISES NSVIMMSSVE 400
    NSRHSSPAGG PRGRLHGLGG PRDNSFLRHA RETPDSYRDS PHSERYVSAM 450
    TTPARMSPVD FHTPSSPKSP PSEMSPPVSS MTVSMPSVAV SPFVEEERPL 500
    LLVTPPRLRE KKYDHHPQQL NSFHHNPAHQ STSLPPSPLR IVEDEEYETT 550
    QEYESVQEPV KKVTNSRRAK RTKPNGHIAN RLEMDSNTSS VSSNSESETE 600
    DERVGEDTPF LGIQNPLAAS LEVAPAFRLA ESRTNPAGRF STQEELQARL 650
    SSVIANQDPI AV 662
    Length:662
    Mass (Da):73,288
    Last modified:November 1, 1996 - v1
    Checksum:i1C31ABCF2A8EB1D5
    GO
    Isoform Alpha2A (identifier: P43322-2) [UniParc]FASTAAdd to Basket

    Also known as: NDF38

    The sequence of this isoform differs from the canonical sequence as follows:
         213-256: PNEFTGDRCQNYVMASFYMTSRRKRQETEKPLERKLDHSLVKES → QPGFTGARCTENVPMKVQTQE

    Show »
    Length:639
    Mass (Da):70,303
    Checksum:i2A5A97DFCE065176
    GO
    Isoform Alpha2B (identifier: P43322-3) [UniParc]FASTAAdd to Basket

    Also known as: NDF19

    The sequence of this isoform differs from the canonical sequence as follows:
         213-256: PNEFTGDRCQNYVMASFYMTSRRKRQETEKPLERKLDHSLVKES → QPGFTGARCTENVPMKVQTQE
         446-484: YVSAMTTPAR...SPPVSSMTVS → HNLIAELRRN...SSITHLGFIL
         485-662: Missing.

    Show »
    Length:461
    Mass (Da):50,809
    Checksum:iBE384394D3C88841
    GO
    Isoform Alpha2C (identifier: P43322-4) [UniParc]FASTAAdd to Basket

    Also known as: NDF44

    The sequence of this isoform differs from the canonical sequence as follows:
         213-256: PNEFTGDRCQNYVMASFYMTSRRKRQETEKPLERKLDHSLVKES → QPGFTGARCTENVPMKVQTQE
         446-662: Missing.

    Show »
    Length:422
    Mass (Da):46,309
    Checksum:iAD15AECCB42C9C45
    GO
    Isoform Beta1 (identifier: P43322-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         231-257: MTSRRKRQETEKPLERKLDHSLVKESK → KHLGIEFME

    Show »
    Length:644
    Mass (Da):71,081
    Checksum:i2382B5DB8682CE17
    GO
    Isoform Beta2 (identifier: P43322-6) [UniParc]FASTAAdd to Basket

    Also known as: NDF40

    The sequence of this isoform differs from the canonical sequence as follows:
         231-256: Missing.
         325-330: PPENVQ → RVRTRG

    Show »
    Length:636
    Mass (Da):70,185
    Checksum:i2F621966AA232AB9
    GO
    Isoform BetA2A (identifier: P43322-7) [UniParc]FASTAAdd to Basket

    Also known as: NDF22

    The sequence of this isoform differs from the canonical sequence as follows:
         231-256: Missing.

    Show »
    Length:636
    Mass (Da):70,123
    Checksum:i995A0710F6F48763
    GO
    Isoform Beta3 (identifier: P43322-8) [UniParc]FASTAAdd to Basket

    Also known as: NDF4

    The sequence of this isoform differs from the canonical sequence as follows:
         231-241: MTSRRKRQETE → STSTPFLSLPE
         242-662: Missing.

    Show »
    Length:241
    Mass (Da):26,213
    Checksum:i556F9540DD94B32B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti90 – 901K → N AA sequence (PubMed:1349853)Curated
    Sequence conflicti137 – 1371T → I AA sequence (PubMed:1349853)Curated
    Sequence conflicti208 – 2081Y → S AA sequence (PubMed:1349853)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei213 – 25644PNEFT…LVKES → QPGFTGARCTENVPMKVQTQ E in isoform Alpha2A, isoform Alpha2B and isoform Alpha2C. 1 PublicationVSP_003436Add
    BLAST
    Alternative sequencei231 – 25727MTSRR…VKESK → KHLGIEFME in isoform Beta1. CuratedVSP_003437Add
    BLAST
    Alternative sequencei231 – 25626Missing in isoform Beta2 and isoform BetA2A. CuratedVSP_003440Add
    BLAST
    Alternative sequencei231 – 24111MTSRRKRQETE → STSTPFLSLPE in isoform Beta3. CuratedVSP_003438Add
    BLAST
    Alternative sequencei242 – 662421Missing in isoform Beta3. CuratedVSP_003439Add
    BLAST
    Alternative sequencei325 – 3306PPENVQ → RVRTRG in isoform Beta2. CuratedVSP_003441
    Alternative sequencei446 – 662217Missing in isoform Alpha2C. 1 PublicationVSP_003442Add
    BLAST
    Alternative sequencei446 – 48439YVSAM…SMTVS → HNLIAELRRNKAYRSKCMQI QLSATHLRPSSITHLGFIL in isoform Alpha2B. CuratedVSP_003443Add
    BLAST
    Alternative sequencei485 – 662178Missing in isoform Alpha2B. CuratedVSP_003444Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U02315 mRNA. Translation: AAA19940.1.
    U02316 mRNA. Translation: AAA19941.1.
    U02317 mRNA. Translation: AAA19942.1.
    U02318 mRNA. Translation: AAA19943.1.
    U02319 mRNA. Translation: AAA19944.1.
    U02320 mRNA. Translation: AAA19945.1.
    U02321 mRNA. Translation: AAA19946.1.
    U02322 mRNA. Translation: AAA19947.1.
    U02323 mRNA. Translation: AAA19948.1.
    U02324 mRNA. Translation: AAA19949.1.
    M92430 mRNA. No translation available.
    PIRiI61718.
    I61719.
    I61722.
    RefSeqiNP_001258052.1. NM_001271123.1. [P43322-8]
    UniGeneiRn.37438.

    Genome annotation databases

    GeneIDi112400.
    KEGGirno:112400.
    UCSCiRGD:621341. rat. [P43322-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U02315 mRNA. Translation: AAA19940.1 .
    U02316 mRNA. Translation: AAA19941.1 .
    U02317 mRNA. Translation: AAA19942.1 .
    U02318 mRNA. Translation: AAA19943.1 .
    U02319 mRNA. Translation: AAA19944.1 .
    U02320 mRNA. Translation: AAA19945.1 .
    U02321 mRNA. Translation: AAA19946.1 .
    U02322 mRNA. Translation: AAA19947.1 .
    U02323 mRNA. Translation: AAA19948.1 .
    U02324 mRNA. Translation: AAA19949.1 .
    M92430 mRNA. No translation available.
    PIRi I61718.
    I61719.
    I61722.
    RefSeqi NP_001258052.1. NM_001271123.1. [P43322-8 ]
    UniGenei Rn.37438.

    3D structure databases

    ProteinModelPortali P43322.
    SMRi P43322. Positions 177-225.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-4996739.

    PTM databases

    PhosphoSitei P43322.

    Proteomic databases

    PaxDbi P43322.
    PRIDEi P43322.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 112400.
    KEGGi rno:112400.
    UCSCi RGD:621341. rat. [P43322-1 ]

    Organism-specific databases

    CTDi 3084.
    RGDi 621341. Nrg1.

    Phylogenomic databases

    eggNOGi NOG47801.
    HOVERGENi HBG006531.
    KOi K05455.
    PhylomeDBi P43322.

    Miscellaneous databases

    NextBioi 617943.

    Gene expression databases

    Genevestigatori P43322.

    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. "Structural and functional aspects of the multiplicity of Neu differentiation factors."
      Wen D., Suggs S.V., Karunagaran D., Liu N., Cupples R.L., Luo Y., Janssen A.M., Ben-Baruch N., Trollinger D.B., Jacobsen V.L., Meng S.-Y., Lu H.S., Hu S., Chang D., Yang W., Yanigahara D., Koski R.A., Yarden Y.
      Mol. Cell. Biol. 14:1909-1919(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
      Tissue: Fibroblast.
    2. "Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit."
      Wen D., Peles E., Cupples R., Suggs S.V., Bacus S.S., Luo Y., Trail G., Hu S., Silbiger S.M., Levy R.B., Koski R.A., Lu H.S., Yarden Y.
      Cell 69:559-572(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA2C), PARTIAL PROTEIN SEQUENCE.
      Tissue: Fibroblast.
    3. "Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells."
      Peles E., Bacus S.S., Koski R.A., Lu H.S., Wen D., Ogden S.G., Levy R.B., Yarden Y.
      Cell 69:205-216(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 14-36.
    4. "Release of the neuregulin functional polypeptide requires its cytoplasmic tail."
      Liu X., Hwang H., Cao L., Wen D., Liu N., Graham R.M., Zhou M.
      J. Biol. Chem. 273:34335-34340(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: REGULATION OF PROCESSING (ISOFORM ALPHA2C).
    5. "Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition."
      Wang J.Y., Frenzel K.E., Wen D., Falls D.L.
      J. Biol. Chem. 273:20525-20534(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LIMK1.
    6. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
      Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
      Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. "Stimulated ErbB4 internalization is necessary for neuregulin signaling in neurons."
      Liu Y., Tao Y.M., Woo R.S., Xiong W.C., Mei L.
      Biochem. Biophys. Res. Commun. 354:505-510(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiNRG1_RAT
    AccessioniPrimary (citable) accession number: P43322
    Secondary accession number(s): P43323
    , P43324, P43325, P43326, P43327, P43328
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 128 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