P56975 · NRG3_HUMAN

  • Protein
    Pro-neuregulin-3, membrane-bound isoform
  • Gene
    NRG3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Direct ligand for the ERBB4 tyrosine kinase receptor. Binding results in ligand-stimulated tyrosine phosphorylation and activation of the receptor. Does not bind to the EGF receptor, ERBB2 or ERBB3 receptors. May be a survival factor for oligodendrocytes.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentextracellular region
Cellular Componentextracellular space
Cellular Componentglutamatergic synapse
Cellular Componentplasma membrane
Molecular Functionchemorepellent activity
Molecular Functiongrowth factor activity
Molecular Functionreceptor ligand activity
Molecular Functionreceptor tyrosine kinase binding
Molecular Functiontransmembrane receptor protein tyrosine kinase activator activity
Biological Processanimal organ development
Biological Processchemorepulsion involved in interneuron migration from the subpallium to the cortex
Biological ProcessERBB4 signaling pathway
Biological ProcessERBB4-ERBB4 signaling pathway
Biological Processintracellular signal transduction
Biological Processmammary placode formation
Biological Processmodulation of chemical synaptic transmission
Biological Processnegative regulation of neuron migration
Biological Processpattern specification process
Biological Processregulation of cell growth
Biological Processsynapse assembly

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Pro-neuregulin-3, membrane-bound isoform
  • Short names
    Pro-NRG3
  • Cleaved into 1 chains

Gene names

    • Name
      NRG3

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P56975
  • Secondary accessions
    • A4D7U1
    • Q0PEH2
    • Q5VYH3

Proteomes

Organism-specific databases

Subcellular Location

Pro-neuregulin-3, membrane-bound isoform

Cell membrane
; Single-pass type I membrane protein
Note: Does not seem to be active.

Neuregulin-3

Secreted

Isoform 3

Cell membrane ; Single-pass type I membrane protein
Note: Isoform 3 is also proteolytically released as a soluble form.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-360Extracellular
Transmembrane361-381Helical; Note=Internal signal sequence
Topological domain382-720Cytoplasmic

Keywords

Disease & Variants

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_047386472in dbSNP:rs2295934
Natural variantVAR_047387552in dbSNP:rs17101193

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 1,183 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain, disulfide bond, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
ChainPRO_00000194821-359UniProtNeuregulin-3
ChainPRO_00000194811-720UniProtPro-neuregulin-3, membrane-bound isoform
Disulfide bond290↔304UniProt
Disulfide bond298↔317UniProt
Disulfide bond319↔328UniProt
Modified residue (large scale data)483PRIDEPhosphoserine

Post-translational modification

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).
Isoform 3 is glycosylated.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in most regions of the brain with the exception of corpus callosum. Expressed at lower level in testis. Not detected in heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, ovary, small intestine, colon and peripheral blood leukocytes.

Developmental stage

Isoform 3 is expressed in fetal brain but not in other fetal tissues.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with ERBB4.

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias, domain.

TypeIDPosition(s)Description
Region28-48Disordered
Region119-223Disordered
Compositional bias121-163Polar residues
Compositional bias179-223Polar residues
Compositional bias246-278Polar residues
Region246-280Disordered
Domain286-329EGF-like
Region451-481Disordered

Domain

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).
ERBB receptor binding is elicited entirely by the EGF-like domain.

Sequence similarities

Belongs to the neuregulin family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (4)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 4 isoforms produced by Alternative splicing.

P56975-1

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.

  • Length
    720
  • Mass (Da)
    77,901
  • Last updated
    2000-12-01 v1
  • Checksum
    A4D6F10DDB95A693
MSEGAAAASPPGAASAAAASAEEGTAAAAAAAAAGGGPDGGGEGAAEPPRELRCSDCIVWNRQQTWLCVVPLFIGFIGLGLSLMLLKWIVVGSVKEYVPTDLVDSKGMGQDPFFLSKPSSFPKAMETTTTTTSTTSPATPSAGGAASSRTPNRISTRLTTITRAPTRFPGHRVPIRASPRSTTARNTAAPATVPSTTAPFFSSSTLGSRPPVPGTPSTQAMPSWPTAAYATSSYLHDSTPSWTLSPFQDAASSSSSSSSSATTTTPETSTSPKFHTTTYSTERSEHFKPCRDKDLAYCLNDGECFVIETLTGSHKHCRCKEGYQGVRCDQFLPKTDSILSDPTDHLGIEFMESEEVYQRQVLSISCIIFGIVIVGMFCAAFYFKSKKQAKQIQEQLKVPQNGKSYSLKASSTMAKSENLVKSHVQLQNYSKVERHPVTALEKMMESSFVGPQSFPEVPSPDRGSQSVKHHRSLSSCCSPGQRSGMLHRNAFRRTPPSPRSRLGGIVGPAYQQLEESRIPDQDTIPCQGIEVRKTISHLPIQLWCVERPLDLKYSSSGLKTQRNTSINMQLPSRETNPYFNSLEQKDLVGYSSTRASSVPIIPSVGLEETCLQMPGISEVKSIKWCKNSYSADVVNVSIPVSDCLIAEQQEVKILLETVQEQIRILTDARRSEDYELASVETEDSASENTAFLPLSPTAKSEREAQFVLRNEIQRDSALTK

P56975-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P56975-3

  • Name
    3
  • Synonyms
    FBNRG3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-221: Missing
    • 222-275: PSWPTAAYATSSYLHDSTPSWTLSPFQDAASSSSSSSSSATTTTPETSTSPKFH → MECGIPPTLVCVGRGGGLHTINIIIWYYFPSAWRTCFNISSSVGLLLTNSYKFY

P56975-4

  • Name
    4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
D9ZHQ3D9ZHQ3_HUMANNRG376
D9ZHQ6D9ZHQ6_HUMANNRG3500
D9ZHQ7D9ZHQ7_HUMANNRG3526
D9ZHQ8D9ZHQ8_HUMANNRG3346
R4GNI6R4GNI6_HUMANNRG354

Features

Showing features for alternative sequence, compositional bias.

TypeIDPosition(s)Description
Alternative sequenceVSP_0218281-221in isoform 3
Compositional bias121-163Polar residues
Compositional bias179-223Polar residues
Alternative sequenceVSP_021829222-275in isoform 3
Compositional bias246-278Polar residues
Alternative sequenceVSP_021830471-477in isoform 2
Alternative sequenceVSP_035752529-552in isoform 4

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ857894
EMBL· GenBank· DDBJ
ABG77979.1
EMBL· GenBank· DDBJ
mRNA
DQ001411
EMBL· GenBank· DDBJ
AAY17216.1
EMBL· GenBank· DDBJ
mRNA
AL096706
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL136085
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL354749
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL391478
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL513204
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL589782
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

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