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P56975 (NRG3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pro-neuregulin-3, membrane-bound isoform

Short name=Pro-NRG3

Cleaved into the following chain:

  1. Neuregulin-3
    Short name=NRG-3
Gene names
Name:NRG3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length720 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.2

Subunit structure

Interacts with ERBB4. Ref.5

Subcellular location

Pro-neuregulin-3, membrane-bound isoform: Cell membrane; Single-pass type I membrane protein By similarity. Note: Does not seem to be active By similarity. Ref.2

Neuregulin-3: Secreted By similarity Ref.2.

Isoform 3: Cell membrane; Single-pass type I membrane protein. Note: Isoform 3 is also proteolytically released as a soluble form. Ref.2

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. Ref.2

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 By similarity.

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. Ref.2

Sequence similarities

Belongs to the neuregulin family.

Contains 1 EGF-like domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: P56975-2)

The sequence of this isoform differs from the canonical sequence as follows:
     471-477: Missing.
Isoform 3 (identifier: P56975-3)

Also known as: FBNRG3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-221: Missing.
     222-275: PSWPTAAYAT...PETSTSPKFH → MECGIPPTLV...LLLTNSYKFY
Isoform 4 (identifier: P56975-4)

The sequence of this isoform differs from the canonical sequence as follows:
     529-552: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 720720Pro-neuregulin-3, membrane-bound isoform
PRO_0000019481
Chain1 – 359359Neuregulin-3
PRO_0000019482

Regions

Topological domain1 – 360360Extracellular Potential
Transmembrane361 – 38121Helical; Note=Internal signal sequence; Potential
Topological domain382 – 720339Cytoplasmic Potential
Domain286 – 32944EGF-like
Compositional bias5 – 84Poly-Ala
Compositional bias13 – 219Poly-Ala
Compositional bias26 – 349Poly-Ala
Compositional bias105 – 285181Ser/Thr-rich
Compositional bias127 – 1359Poly-Thr
Compositional bias252 – 2609Poly-Ser
Compositional bias262 – 2654Poly-Thr

Amino acid modifications

Disulfide bond290 ↔ 304 By similarity
Disulfide bond298 ↔ 317 By similarity
Disulfide bond319 ↔ 328 By similarity

Natural variations

Alternative sequence1 – 221221Missing in isoform 3.
VSP_021828
Alternative sequence222 – 27554PSWPT…SPKFH → MECGIPPTLVCVGRGGGLHT INIIIWYYFPSAWRTCFNIS SSVGLLLTNSYKFY in isoform 3.
VSP_021829
Alternative sequence471 – 4777Missing in isoform 2.
VSP_021830
Alternative sequence529 – 55224Missing in isoform 4.
VSP_035752
Natural variant4721S → R.
Corresponds to variant rs2295934 [ dbSNP | Ensembl ].
VAR_047386
Natural variant5521K → N.
Corresponds to variant rs17101193 [ dbSNP | Ensembl ].
VAR_047387

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2000. Version 1.
Checksum: A4D6F10DDB95A693

FASTA72077,901
        10         20         30         40         50         60 
MSEGAAAASP PGAASAAAAS AEEGTAAAAA AAAAGGGPDG GGEGAAEPPR ELRCSDCIVW 

        70         80         90        100        110        120 
NRQQTWLCVV PLFIGFIGLG LSLMLLKWIV VGSVKEYVPT DLVDSKGMGQ DPFFLSKPSS 

       130        140        150        160        170        180 
FPKAMETTTT TTSTTSPATP SAGGAASSRT PNRISTRLTT ITRAPTRFPG HRVPIRASPR 

       190        200        210        220        230        240 
STTARNTAAP ATVPSTTAPF FSSSTLGSRP PVPGTPSTQA MPSWPTAAYA TSSYLHDSTP 

       250        260        270        280        290        300 
SWTLSPFQDA ASSSSSSSSS ATTTTPETST SPKFHTTTYS TERSEHFKPC RDKDLAYCLN 

       310        320        330        340        350        360 
DGECFVIETL TGSHKHCRCK EGYQGVRCDQ FLPKTDSILS DPTDHLGIEF MESEEVYQRQ 

       370        380        390        400        410        420 
VLSISCIIFG IVIVGMFCAA FYFKSKKQAK QIQEQLKVPQ NGKSYSLKAS STMAKSENLV 

       430        440        450        460        470        480 
KSHVQLQNYS KVERHPVTAL EKMMESSFVG PQSFPEVPSP DRGSQSVKHH RSLSSCCSPG 

       490        500        510        520        530        540 
QRSGMLHRNA FRRTPPSPRS RLGGIVGPAY QQLEESRIPD QDTIPCQGIE VRKTISHLPI 

       550        560        570        580        590        600 
QLWCVERPLD LKYSSSGLKT QRNTSINMQL PSRETNPYFN SLEQKDLVGY SSTRASSVPI 

       610        620        630        640        650        660 
IPSVGLEETC LQMPGISEVK SIKWCKNSYS ADVVNVSIPV SDCLIAEQQE VKILLETVQE 

       670        680        690        700        710        720 
QIRILTDARR SEDYELASVE TEDSASENTA FLPLSPTAKS EREAQFVLRN EIQRDSALTK 

« Hide

Isoform 2 [UniParc].

Checksum: 1D5F8D4FA3A138FC
Show »

FASTA71377,164
Isoform 3 (FBNRG3) [UniParc].

Checksum: 6093904545F28F94
Show »

FASTA49956,034
Isoform 4 [UniParc].

Checksum: 1823F048DB30043C
Show »

FASTA69675,031

References

« Hide 'large scale' references
[1]"Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4."
Zhang D., Sliwkowski M.X., Mark M., Frantz G., Akita R., Sun Y., Hillan K., Crowley C., Brush J., Godowski P.J.
Proc. Natl. Acad. Sci. U.S.A. 94:9562-9567(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
Tissue: Fetal brain.
[2]"Characterization of a neural-specific splicing form of the human neuregulin 3 gene involved in oligodendrocyte survival."
Carteron C., Ferrer-Montiel A.V., Cabedo H.
J. Cell Sci. 119:898-909(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, GLYCOSYLATION, FUNCTION.
Tissue: Fetal brain.
[3]"Bi-directional signalling by NRG-3 cytoplasmic domain."
Tiao J.Y., Busfield S.J.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Ligand discrimination in signaling through an ErbB4 receptor homodimer."
Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C., Carraway K.L. III
J. Biol. Chem. 275:19803-19807(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ERBB4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ857894 mRNA. Translation: ABG77979.1.
DQ001411 mRNA. Translation: AAY17216.1.
AL354749 expand/collapse EMBL AC list , AL096706, AL136085, AL391478, AL513204, AL589782 Genomic DNA. Translation: CAH70641.1.
AL136085 expand/collapse EMBL AC list , AL096706, AL354749, AL391478, AL513204, AL589782 Genomic DNA. Translation: CAH71050.1.
AL513204 expand/collapse EMBL AC list , AL096706, AL136085, AL354749, AL391478, AL589782 Genomic DNA. Translation: CAH73645.1.
AL391478 expand/collapse EMBL AC list , AL096706, AL136085, AL354749, AL513204, AL589782 Genomic DNA. Translation: CAI15622.1.
AL589782 expand/collapse EMBL AC list , AL096706, AL136085, AL354749, AL391478, AL513204 Genomic DNA. Translation: CAI17213.1.
AL096706 expand/collapse EMBL AC list , AL136085, AL354749, AL391478, AL513204, AL589782 Genomic DNA. Translation: CAI22410.1.
RefSeqNP_001010848.2. NM_001010848.3.
NP_001159445.1. NM_001165973.1.
XP_005269501.1. XM_005269444.2.
UniGeneHs.125119.

3D structure databases

ProteinModelPortalP56975.
SMRP56975. Positions 283-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000361214.

PTM databases

PhosphoSiteP56975.

Polymorphism databases

DMDM9789758.

Proteomic databases

PaxDbP56975.
PRIDEP56975.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372141; ENSP00000361214; ENSG00000185737. [P56975-4]
ENST00000372142; ENSP00000361215; ENSG00000185737. [P56975-3]
ENST00000404547; ENSP00000384796; ENSG00000185737. [P56975-1]
GeneID10718.
KEGGhsa:10718.
UCSCuc001kco.2. human. [P56975-4]
uc001kcp.2. human. [P56975-3]
uc001kcr.2. human. [P56975-1]

Organism-specific databases

CTD10718.
GeneCardsGC10P083625.
HGNCHGNC:7999. NRG3.
HPAHPA038206.
MIM605533. gene.
neXtProtNX_P56975.
PharmGKBPA31778.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40523.
HOGENOMHOG000113852.
HOVERGENHBG006532.
InParanoidP56975.
KOK05457.
OrthoDBEOG7SR4KZ.
PhylomeDBP56975.
TreeFamTF336537.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP56975.

Gene expression databases

ArrayExpressP56975.
BgeeP56975.
CleanExHS_NRG3.
GenevestigatorP56975.

Family and domain databases

InterProIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
[Graphical view]
SMARTSM00181. EGF. 1 hit.
[Graphical view]
PROSITEPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNRG3.
GenomeRNAi10718.
NextBio40693.
PROP56975.
SOURCESearch...

Entry information

Entry nameNRG3_HUMAN
AccessionPrimary (citable) accession number: P56975
Secondary accession number(s): A4D7U1, Q0PEH2, Q5VYH3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM