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Protein

Pro-neuregulin-4, membrane-bound isoform

Gene

NRG4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiREACT_115596. Signaling by ERBB4.
REACT_115755. Signaling by ERBB2.
REACT_115854. GRB2 events in ERBB2 signaling.
REACT_115961. PI3K events in ERBB4 signaling.
REACT_115993. SHC1 events in ERBB2 signaling.
REACT_116005. SHC1 events in ERBB4 signaling.
REACT_116008. PI3K events in ERBB2 signaling.
REACT_116022. Nuclear signaling by ERBB4.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_75829. PIP3 activates AKT signaling.
SignaLinkiQ8WWG1.

Names & Taxonomyi

Protein namesi
Recommended name:
Pro-neuregulin-4, membrane-bound isoform
Short name:
Pro-NRG4
Cleaved into the following chain:
Neuregulin-4
Short name:
NRG-4
Gene namesi
Name:NRG4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:29862. NRG4.

Subcellular locationi

Pro-neuregulin-4, membrane-bound isoform :
Neuregulin-4 :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6262ExtracellularSequence AnalysisAdd
BLAST
Transmembranei63 – 8321Helical; Note=Internal signal sequenceSequence AnalysisAdd
BLAST
Topological domaini84 – 11532CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142671246.

Polymorphism and mutation databases

BioMutaiNRG4.
DMDMi28201832.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 115115Pro-neuregulin-4, membrane-bound isoformPRO_0000019485Add
BLAST
Chaini1 – 6161Neuregulin-4PRO_0000019486Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi9 ↔ 23PROSITE-ProRule annotation
Disulfide bondi17 ↔ 34PROSITE-ProRule annotation
Disulfide bondi36 ↔ 45PROSITE-ProRule annotation
Glycosylationi39 – 391N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiQ8WWG1.

Expressioni

Gene expression databases

BgeeiQ8WWG1.
CleanExiHS_NRG4.
ExpressionAtlasiQ8WWG1. baseline and differential.
GenevisibleiQ8WWG1. HS.

Organism-specific databases

HPAiHPA010957.

Interactioni

Subunit structurei

Interacts with ERBB4.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
FATE1Q969F04EBI-8637292,EBI-743099

Protein-protein interaction databases

BioGridi126957. 1 interaction.
IntActiQ8WWG1. 2 interactions.
STRINGi9606.ENSP00000378367.

Structurei

3D structure databases

ProteinModelPortaliQ8WWG1.
SMRiQ8WWG1. Positions 3-47.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 4642EGF-likePROSITE-ProRule annotationAdd
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.By similarity

Sequence similaritiesi

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

Keywords - Domaini

EGF-like domain, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42904.
GeneTreeiENSGT00390000014815.
HOGENOMiHOG000113853.
HOVERGENiHBG006533.
InParanoidiQ8WWG1.
KOiK05458.
OMAiFLCRKGH.
OrthoDBiEOG73806M.
PhylomeDBiQ8WWG1.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
[Graphical view]
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8WWG1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTDHEEPCG PSHKSFCLNG GLCYVIPTIP SPFCRCVENY TGARCEEVFL
60 70 80 90 100
PGSSIQTKSN LFEAFVALAV LVTLIIGAFY FLCRKGHFQR ASSVQYDINL
110
VETSSTSAHH SHEQH
Length:115
Mass (Da):12,722
Last modified:March 1, 2002 - v1
Checksum:i72F962E2D0F37AC3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC087456 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99227.1.
BC017568 mRNA. Translation: AAH17568.1.
CCDSiCCDS10288.1.
RefSeqiNP_612640.1. NM_138573.3.
UniGeneiHs.732438.

Genome annotation databases

EnsembliENST00000394907; ENSP00000378367; ENSG00000169752.
ENST00000566417; ENSP00000457335; ENSG00000169752.
GeneIDi145957.
KEGGihsa:145957.
UCSCiuc002bbo.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC087456 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99227.1.
BC017568 mRNA. Translation: AAH17568.1.
CCDSiCCDS10288.1.
RefSeqiNP_612640.1. NM_138573.3.
UniGeneiHs.732438.

3D structure databases

ProteinModelPortaliQ8WWG1.
SMRiQ8WWG1. Positions 3-47.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126957. 1 interaction.
IntActiQ8WWG1. 2 interactions.
STRINGi9606.ENSP00000378367.

Polymorphism and mutation databases

BioMutaiNRG4.
DMDMi28201832.

Proteomic databases

PRIDEiQ8WWG1.

Protocols and materials databases

DNASUi145957.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000394907; ENSP00000378367; ENSG00000169752.
ENST00000566417; ENSP00000457335; ENSG00000169752.
GeneIDi145957.
KEGGihsa:145957.
UCSCiuc002bbo.3. human.

Organism-specific databases

CTDi145957.
GeneCardsiGC15M076233.
HGNCiHGNC:29862. NRG4.
HPAiHPA010957.
MIMi610894. gene.
neXtProtiNX_Q8WWG1.
PharmGKBiPA142671246.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG42904.
GeneTreeiENSGT00390000014815.
HOGENOMiHOG000113853.
HOVERGENiHBG006533.
InParanoidiQ8WWG1.
KOiK05458.
OMAiFLCRKGH.
OrthoDBiEOG73806M.
PhylomeDBiQ8WWG1.

Enzyme and pathway databases

ReactomeiREACT_115596. Signaling by ERBB4.
REACT_115755. Signaling by ERBB2.
REACT_115854. GRB2 events in ERBB2 signaling.
REACT_115961. PI3K events in ERBB4 signaling.
REACT_115993. SHC1 events in ERBB2 signaling.
REACT_116005. SHC1 events in ERBB4 signaling.
REACT_116008. PI3K events in ERBB2 signaling.
REACT_116022. Nuclear signaling by ERBB4.
REACT_147727. Constitutive Signaling by Aberrant PI3K in Cancer.
REACT_75829. PIP3 activates AKT signaling.
SignaLinkiQ8WWG1.

Miscellaneous databases

ChiTaRSiNRG4. human.
GeneWikiiNRG4.
GenomeRNAii145957.
NextBioi85235.
PROiQ8WWG1.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WWG1.
CleanExiHS_NRG4.
ExpressionAtlasiQ8WWG1. baseline and differential.
GenevisibleiQ8WWG1. HS.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
[Graphical view]
SMARTiSM00181. EGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Liver.

Entry informationi

Entry nameiNRG4_HUMAN
AccessioniPrimary (citable) accession number: Q8WWG1
Secondary accession number(s): A6NIE8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2003
Last sequence update: March 1, 2002
Last modified: July 22, 2015
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.