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Q8WWG1

- NRG4_HUMAN

UniProt

Q8WWG1 - NRG4_HUMAN

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Protein
Pro-neuregulin-4, membrane-bound isoform
Gene
NRG4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at transcript 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.

GO - Biological processi

  1. Fc-epsilon receptor signaling pathway Source: Reactome
  2. epidermal growth factor receptor signaling pathway Source: Reactome
  3. fibroblast growth factor receptor signaling pathway Source: Reactome
  4. innate immune response Source: Reactome
  5. neurotrophin TRK receptor signaling pathway Source: Reactome
  6. phosphatidylinositol-mediated signaling Source: Reactome
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 PI3K/AKT Signaling 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: Chromosome 15

Organism-specific databases

HGNCiHGNC:29862. NRG4.

Subcellular locationi

Chain Pro-neuregulin-4, membrane-bound isoform : Cell membrane; Single-pass type I membrane protein By similarity
Note: Does not seem to be active By similarity.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6262Extracellular Reviewed prediction
Add
BLAST
Transmembranei63 – 8321Helical; Note=Internal signal sequence; Reviewed prediction
Add
BLAST
Topological domaini84 – 11532Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142671246.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 115115Pro-neuregulin-4, membrane-bound isoform
PRO_0000019485Add
BLAST
Chaini1 – 6161Neuregulin-4
PRO_0000019486Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi9 ↔ 23 By similarity
Disulfide bondi17 ↔ 34 By similarity
Disulfide bondi36 ↔ 45 By similarity
Glycosylationi39 – 391N-linked (GlcNAc...) Reviewed prediction

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

ArrayExpressiQ8WWG1.
BgeeiQ8WWG1.
CleanExiHS_NRG4.
GenevestigatoriQ8WWG1.

Organism-specific databases

HPAiHPA010957.

Interactioni

Subunit structurei

Interacts with ERBB4 By similarity.

Protein-protein interaction databases

IntActiQ8WWG1. 2 interactions.
STRINGi9606.ENSP00000378367.

Structurei

3D structure databases

ProteinModelPortaliQ8WWG1.
SMRiQ8WWG1. Positions 15-46.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 4642EGF-like
Add
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.
ERBB receptor binding is elicited entirely by the EGF-like domain By similarity.

Sequence similaritiesi

Belongs to the neuregulin family.
Contains 1 EGF-like domain.

Keywords - Domaini

EGF-like domain, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42904.
HOGENOMiHOG000113853.
HOVERGENiHBG006533.
InParanoidiQ8WWG1.
KOiK05458.
OMAiPMENKLA.
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

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MPTDHEEPCG PSHKSFCLNG GLCYVIPTIP SPFCRCVENY TGARCEEVFL    50
PGSSIQTKSN LFEAFVALAV LVTLIIGAFY FLCRKGHFQR ASSVQYDINL 100
VETSSTSAHH SHEQH 115
Length:115
Mass (Da):12,722
Last modified:March 1, 2002 - v1
Checksum:i72F962E2D0F37AC3
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi28201832.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC087456 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99227.1 .
BC017568 mRNA. Translation: AAH17568.1 .
CCDSi CCDS10288.1.
RefSeqi NP_612640.1. NM_138573.3.
UniGenei Hs.732438.

3D structure databases

ProteinModelPortali Q8WWG1.
SMRi Q8WWG1. Positions 15-46.
ModBasei Search...

Protein-protein interaction databases

IntActi Q8WWG1. 2 interactions.
STRINGi 9606.ENSP00000378367.

Polymorphism databases

DMDMi 28201832.

Proteomic databases

PRIDEi Q8WWG1.

Protocols and materials databases

DNASUi 145957.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000394907 ; ENSP00000378367 ; ENSG00000169752 .
ENST00000566417 ; ENSP00000457335 ; ENSG00000169752 .
GeneIDi 145957.
KEGGi hsa:145957.
UCSCi uc002bbo.3. human.

Organism-specific databases

CTDi 145957.
GeneCardsi GC15M076233.
HGNCi HGNC:29862. NRG4.
HPAi HPA010957.
MIMi 610894. gene.
neXtProti NX_Q8WWG1.
PharmGKBi PA142671246.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG42904.
HOGENOMi HOG000113853.
HOVERGENi HBG006533.
InParanoidi Q8WWG1.
KOi K05458.
OMAi PMENKLA.
OrthoDBi EOG73806M.
PhylomeDBi Q8WWG1.

Enzyme and pathway databases

Reactomei REACT_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 PI3K/AKT Signaling in Cancer.
REACT_75829. PIP3 activates AKT signaling.
SignaLinki Q8WWG1.

Miscellaneous databases

GeneWikii NRG4.
GenomeRNAii 145957.
NextBioi 85235.
PROi Q8WWG1.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8WWG1.
Bgeei Q8WWG1.
CleanExi HS_NRG4.
Genevestigatori Q8WWG1.

Family and domain databases

InterProi IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
[Graphical view ]
SMARTi SM00181. EGF. 1 hit.
[Graphical view ]
PROSITEi PS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 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
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

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