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P56975

- NRG3_HUMAN

UniProt

P56975 - NRG3_HUMAN

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Protein

Pro-neuregulin-3, membrane-bound isoform

Gene
NRG3
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. growth factor activity Source: UniProtKB
  2. receptor tyrosine kinase binding Source: UniProtKB
  3. transmembrane receptor protein tyrosine kinase activator activity Source: UniProtKB

GO - Biological processi

  1. activation of transmembrane receptor protein tyrosine kinase activity Source: GOC
  2. mammary placode formation Source: Ensembl
  3. pattern specification process Source: Ensembl
  4. regulation of cell growth Source: UniProtKB
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.
SignaLinkiP56975.

Names & Taxonomyi

Protein namesi
Recommended name:
Pro-neuregulin-3, membrane-bound isoform
Short name:
Pro-NRG3
Cleaved into the following chain:
Neuregulin-3
Short name:
NRG-3
Gene namesi
Name:NRG3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:7999. NRG3.

Subcellular locationi

Chain 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.1 Publication
Chain Neuregulin-3 : Secreted By similarity 1 Publication
Isoform 3 : Cell membrane; Single-pass type I membrane protein
Note: Isoform 3 is also proteolytically released as a soluble form.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 360360Extracellular Reviewed predictionAdd
BLAST
Transmembranei361 – 38121Helical; Note=Internal signal sequence; Reviewed predictionAdd
BLAST
Topological domaini382 – 720339Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. extracellular region Source: UniProtKB
  2. integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31778.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 720720Pro-neuregulin-3, membrane-bound isoformPRO_0000019481Add
BLAST
Chaini1 – 359359Neuregulin-3PRO_0000019482Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi290 ↔ 304 By similarity
Disulfide bondi298 ↔ 317 By similarity
Disulfide bondi319 ↔ 328 By 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.
Extensive glycosylation precedes the proteolytic cleavage By similarity. Isoform 3 is glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP56975.
PRIDEiP56975.

PTM databases

PhosphoSiteiP56975.

Expressioni

Tissue specificityi

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 stagei

Isoform 3 is expressed in fetal brain but not in other fetal tissues.1 Publication

Gene expression databases

ArrayExpressiP56975.
BgeeiP56975.
CleanExiHS_NRG3.
GenevestigatoriP56975.

Organism-specific databases

HPAiHPA038206.

Interactioni

Subunit structurei

Interacts with ERBB4.1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000361214.

Structurei

3D structure databases

ProteinModelPortaliP56975.
SMRiP56975. Positions 286-333.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini286 – 32944EGF-likeAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi5 – 84Poly-Ala
Compositional biasi13 – 219Poly-Ala
Compositional biasi26 – 349Poly-Ala
Compositional biasi105 – 285181Ser/Thr-richAdd
BLAST
Compositional biasi127 – 1359Poly-Thr
Compositional biasi252 – 2609Poly-Ser
Compositional biasi262 – 2654Poly-Thr

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

eggNOGiNOG40523.
HOGENOMiHOG000113852.
HOVERGENiHBG006532.
InParanoidiP56975.
KOiK05457.
OrthoDBiEOG7SR4KZ.
PhylomeDBiP56975.
TreeFamiTF336537.

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.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P56975-1) [UniParc]FASTAAdd to Basket

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

MSEGAAAASP PGAASAAAAS AEEGTAAAAA AAAAGGGPDG GGEGAAEPPR    50
ELRCSDCIVW NRQQTWLCVV PLFIGFIGLG LSLMLLKWIV VGSVKEYVPT 100
DLVDSKGMGQ DPFFLSKPSS FPKAMETTTT TTSTTSPATP SAGGAASSRT 150
PNRISTRLTT ITRAPTRFPG HRVPIRASPR STTARNTAAP ATVPSTTAPF 200
FSSSTLGSRP PVPGTPSTQA MPSWPTAAYA TSSYLHDSTP SWTLSPFQDA 250
ASSSSSSSSS ATTTTPETST SPKFHTTTYS TERSEHFKPC RDKDLAYCLN 300
DGECFVIETL TGSHKHCRCK EGYQGVRCDQ FLPKTDSILS DPTDHLGIEF 350
MESEEVYQRQ VLSISCIIFG IVIVGMFCAA FYFKSKKQAK QIQEQLKVPQ 400
NGKSYSLKAS STMAKSENLV KSHVQLQNYS KVERHPVTAL EKMMESSFVG 450
PQSFPEVPSP DRGSQSVKHH RSLSSCCSPG QRSGMLHRNA FRRTPPSPRS 500
RLGGIVGPAY QQLEESRIPD QDTIPCQGIE VRKTISHLPI QLWCVERPLD 550
LKYSSSGLKT QRNTSINMQL PSRETNPYFN SLEQKDLVGY SSTRASSVPI 600
IPSVGLEETC LQMPGISEVK SIKWCKNSYS ADVVNVSIPV SDCLIAEQQE 650
VKILLETVQE QIRILTDARR SEDYELASVE TEDSASENTA FLPLSPTAKS 700
EREAQFVLRN EIQRDSALTK 720
Length:720
Mass (Da):77,901
Last modified:December 1, 2000 - v1
Checksum:iA4D6F10DDB95A693
GO
Isoform 2 (identifier: P56975-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     471-477: Missing.

Show »
Length:713
Mass (Da):77,164
Checksum:i1D5F8D4FA3A138FC
GO
Isoform 3 (identifier: P56975-3) [UniParc]FASTAAdd to Basket

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

Show »
Length:499
Mass (Da):56,034
Checksum:i6093904545F28F94
GO
Isoform 4 (identifier: P56975-4) [UniParc]FASTAAdd to Basket

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

Show »
Length:696
Mass (Da):75,031
Checksum:i1823F048DB30043C
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti472 – 4721S → R.
Corresponds to variant rs2295934 [ dbSNP | Ensembl ].
VAR_047386
Natural varianti552 – 5521K → N.
Corresponds to variant rs17101193 [ dbSNP | Ensembl ].
VAR_047387

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 221221Missing in isoform 3. VSP_021828Add
BLAST
Alternative sequencei222 – 27554PSWPT…SPKFH → MECGIPPTLVCVGRGGGLHT INIIIWYYFPSAWRTCFNIS SSVGLLLTNSYKFY in isoform 3. VSP_021829Add
BLAST
Alternative sequencei471 – 4777Missing in isoform 2. VSP_021830
Alternative sequencei529 – 55224Missing in isoform 4. VSP_035752Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DQ857894 mRNA. Translation: ABG77979.1.
DQ001411 mRNA. Translation: AAY17216.1.
AL354749
, AL096706, AL136085, AL391478, AL513204, AL589782 Genomic DNA. Translation: CAH70641.1.
AL136085
, AL096706, AL354749, AL391478, AL513204, AL589782 Genomic DNA. Translation: CAH71050.1.
AL513204
, AL096706, AL136085, AL354749, AL391478, AL589782 Genomic DNA. Translation: CAH73645.1.
AL391478
, AL096706, AL136085, AL354749, AL513204, AL589782 Genomic DNA. Translation: CAI15622.1.
AL589782
, AL096706, AL136085, AL354749, AL391478, AL513204 Genomic DNA. Translation: CAI17213.1.
AL096706
, AL136085, AL354749, AL391478, AL513204, AL589782 Genomic DNA. Translation: CAI22410.1.
CCDSiCCDS31233.1. [P56975-4]
CCDS53547.1. [P56975-3]
RefSeqiNP_001010848.2. NM_001010848.3. [P56975-4]
NP_001159445.1. NM_001165973.1. [P56975-3]
XP_005269501.1. XM_005269444.2. [P56975-1]
UniGeneiHs.125119.

Genome annotation databases

EnsembliENST00000372141; ENSP00000361214; ENSG00000185737. [P56975-4]
ENST00000372142; ENSP00000361215; ENSG00000185737. [P56975-3]
ENST00000404547; ENSP00000384796; ENSG00000185737. [P56975-1]
GeneIDi10718.
KEGGihsa:10718.
UCSCiuc001kco.2. human. [P56975-4]
uc001kcp.2. human. [P56975-3]
uc001kcr.2. human. [P56975-1]

Polymorphism databases

DMDMi9789758.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
DQ857894 mRNA. Translation: ABG77979.1 .
DQ001411 mRNA. Translation: AAY17216.1 .
AL354749
, AL096706 , AL136085 , AL391478 , AL513204 , AL589782 Genomic DNA. Translation: CAH70641.1 .
AL136085
, AL096706 , AL354749 , AL391478 , AL513204 , AL589782 Genomic DNA. Translation: CAH71050.1 .
AL513204
, AL096706 , AL136085 , AL354749 , AL391478 , AL589782 Genomic DNA. Translation: CAH73645.1 .
AL391478
, AL096706 , AL136085 , AL354749 , AL513204 , AL589782 Genomic DNA. Translation: CAI15622.1 .
AL589782
, AL096706 , AL136085 , AL354749 , AL391478 , AL513204 Genomic DNA. Translation: CAI17213.1 .
AL096706
, AL136085 , AL354749 , AL391478 , AL513204 , AL589782 Genomic DNA. Translation: CAI22410.1 .
CCDSi CCDS31233.1. [P56975-4 ]
CCDS53547.1. [P56975-3 ]
RefSeqi NP_001010848.2. NM_001010848.3. [P56975-4 ]
NP_001159445.1. NM_001165973.1. [P56975-3 ]
XP_005269501.1. XM_005269444.2. [P56975-1 ]
UniGenei Hs.125119.

3D structure databases

ProteinModelPortali P56975.
SMRi P56975. Positions 286-333.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000361214.

PTM databases

PhosphoSitei P56975.

Polymorphism databases

DMDMi 9789758.

Proteomic databases

PaxDbi P56975.
PRIDEi P56975.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000372141 ; ENSP00000361214 ; ENSG00000185737 . [P56975-4 ]
ENST00000372142 ; ENSP00000361215 ; ENSG00000185737 . [P56975-3 ]
ENST00000404547 ; ENSP00000384796 ; ENSG00000185737 . [P56975-1 ]
GeneIDi 10718.
KEGGi hsa:10718.
UCSCi uc001kco.2. human. [P56975-4 ]
uc001kcp.2. human. [P56975-3 ]
uc001kcr.2. human. [P56975-1 ]

Organism-specific databases

CTDi 10718.
GeneCardsi GC10P083625.
HGNCi HGNC:7999. NRG3.
HPAi HPA038206.
MIMi 605533. gene.
neXtProti NX_P56975.
PharmGKBi PA31778.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG40523.
HOGENOMi HOG000113852.
HOVERGENi HBG006532.
InParanoidi P56975.
KOi K05457.
OrthoDBi EOG7SR4KZ.
PhylomeDBi P56975.
TreeFami TF336537.

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 P56975.

Miscellaneous databases

GeneWikii NRG3.
GenomeRNAii 10718.
NextBioi 40693.
PROi P56975.
SOURCEi Search...

Gene expression databases

ArrayExpressi P56975.
Bgeei P56975.
CleanExi HS_NRG3.
Genevestigatori P56975.

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.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiNRG3_HUMAN
AccessioniPrimary (citable) accession number: P56975
Secondary accession number(s): A4D7U1, Q0PEH2, Q5VYH3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: September 3, 2014
This is version 122 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 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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