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Protein

Pro-neuregulin-3, membrane-bound isoform

Gene

Nrg3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.1 Publication

GO - Molecular functioni

  • chemorepellent activity Source: MGI
  • growth factor activity Source: UniProtKB-KW
  • signaling receptor binding Source: GO_Central

GO - Biological processi

  • chemorepulsion involved in interneuron migration from the subpallium to the cortex Source: MGI
  • intracellular signal transduction Source: MGI
  • mammary gland development Source: MGI
  • mammary placode formation Source: MGI
  • negative regulation of neuron migration Source: MGI
  • pattern specification process Source: MGI

Keywordsi

Molecular functionGrowth factor

Enzyme and pathway databases

ReactomeiR-MMU-1227986 Signaling by ERBB2
R-MMU-1236394 Signaling by ERBB4
R-MMU-1250196 SHC1 events in ERBB2 signaling
R-MMU-1250342 PI3K events in ERBB4 signaling
R-MMU-1250347 SHC1 events in ERBB4 signaling
R-MMU-1257604 PIP3 activates AKT signaling
R-MMU-1963640 GRB2 events in ERBB2 signaling
R-MMU-1963642 PI3K events in ERBB2 signaling
R-MMU-5673001 RAF/MAP kinase cascade
R-MMU-6785631 ERBB2 Regulates Cell Motility
R-MMU-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-MMU-8847993 ERBB2 Activates PTK6 Signaling
R-MMU-8863795 Downregulation of ERBB2 signaling

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1097165 Nrg3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 362ExtracellularSequence analysisAdd BLAST362
Transmembranei363 – 383Helical; Note=Internal signal sequenceSequence analysisAdd BLAST21
Topological domaini384 – 713CytoplasmicSequence analysisAdd BLAST330

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000194831 – 713Pro-neuregulin-3, membrane-bound isoformAdd BLAST713
ChainiPRO_00000194841 – 361Neuregulin-3Add BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi292 ↔ 306PROSITE-ProRule annotation
Disulfide bondi300 ↔ 319PROSITE-ProRule annotation
Disulfide bondi321 ↔ 330PROSITE-ProRule annotation

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

Proteomic databases

PaxDbiO35181
PRIDEiO35181

PTM databases

iPTMnetiO35181
PhosphoSitePlusiO35181

Expressioni

Tissue specificityi

Expressed in sympathetic, motor, and sensory neurons.

Developmental stagei

Detected as early as 11 dpc. At 13 dpc detected mainly in the nervous system. At 16 dpc, detected in the brain, spinal cord, trigeminal, vestibular-cochlear, and spinal ganglia. In adults, expressed in spinal cord, and numerous brain regions.

Gene expression databases

BgeeiENSMUSG00000041014
CleanExiMM_NRG3
ExpressionAtlasiO35181 baseline and differential
GenevisibleiO35181 MM

Interactioni

Subunit structurei

Interacts with ERBB4.1 Publication

GO - Molecular functioni

  • chemorepellent activity Source: MGI
  • growth factor activity Source: UniProtKB-KW
  • signaling receptor binding Source: GO_Central

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000136884

Structurei

3D structure databases

ProteinModelPortaliO35181
SMRiO35181
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini288 – 331EGF-likePROSITE-ProRule annotationAdd BLAST44

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi13 – 21Poly-Ala9
Compositional biasi26 – 34Poly-Ala9
Compositional biasi105 – 287Ser/Thr-richAdd BLAST183
Compositional biasi127 – 135Poly-Thr9
Compositional biasi250 – 253Poly-Ala4
Compositional biasi254 – 263Poly-Ser10
Compositional biasi264 – 267Poly-Thr4

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

Keywords - Domaini

EGF-like domain, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IMQB Eukaryota
ENOG4111KAZ LUCA
GeneTreeiENSGT00900000140940
HOVERGENiHBG006532
InParanoidiO35181
KOiK05457
OMAiMMESSFA
OrthoDBiEOG091G07O8
PhylomeDBiO35181
TreeFamiTF336537

Family and domain databases

InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR002154 Neuregulin_C
PfamiView protein in Pfam
PF02158 Neuregulin, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 1 hit
PS50026 EGF_3, 1 hit

Sequencei

Sequence statusi: Complete.

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

O35181-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSEGAAGASP PGAASAAAAS AEEGTAAAAA AAAAGGGPDG GGEGAAEPPR
60 70 80 90 100
ELRCSDCIVW NRQQTWLCVV PLFIGFIGLG LSLMLLKWIV VGSVKEYVPT
110 120 130 140 150
DLVDSKGMGQ DPFFLSKPSS FPKAMETTTT TTSTTSPATP SAGGAASSRT
160 170 180 190 200
PNRISTRLTT ITRAPTRFPG HRVPIRASPR STTARNTAAP PTVLSTTAPF
210 220 230 240 250
FSSSTPGSRP PMPGAPSTQA MPSWPTAAYA TSSYLHDSTP SWTLSPFQDA
260 270 280 290 300
AAASSSSPSS TSSTTTTPET STSPKFHTTT YSTERSEHFK PCRDKDLAYC
310 320 330 340 350
LNDGECFVIE TLTGSHKHCR CKEGYQGVRC DQFLPKTDSI LSDPTDHLGI
360 370 380 390 400
EFMESEDVYQ RQVLSISCII FGIVIVGMFC AAFYFKSKKQ AKQIQEHLKE
410 420 430 440 450
SQNGKNYSLK ASSTKSESLM KSHVHLQNYS KADRHPVTAL EKIMESSFSA
460 470 480 490 500
PQSFPEVTSP DRGSQPIKHH SPGQRSGMLH RNTFRRAPPS PRSRLGGIVG
510 520 530 540 550
PAYQQLEESR IPDQDTIPCQ GIEVRKTISH LPIQLWCVER PLDLKYVSNG
560 570 580 590 600
LRTQQNASIN MQLPSRETNP YFNSLDQKDL VGYLSPRANS VPIIPSMGLE
610 620 630 640 650
ETCMQMPGIS DVKSIKWCKN SYSADIVNAS MPVSDCLLEE QQEVKILLET
660 670 680 690 700
VQEQIRILTD ARRSEDFELA SMETEDSASE NTAFLPLSPT AKSEREAQFV
710
LRNEIQRDSV LTK
Length:713
Mass (Da):77,370
Last modified:January 1, 1998 - v1
Checksum:i9F7D1D5E7FC8DCF0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF010130 mRNA Translation: AAB70914.1
CCDSiCCDS26954.1
PIRiT44447
RefSeqiNP_032760.1, NM_008734.3
UniGeneiMm.258705

Genome annotation databases

EnsembliENSMUST00000166968; ENSMUSP00000136884; ENSMUSG00000041014
GeneIDi18183
KEGGimmu:18183
UCSCiuc007tbz.2 mouse

Similar proteinsi

Entry informationi

Entry nameiNRG3_MOUSE
AccessioniPrimary (citable) accession number: O35181
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: May 23, 2018
This is version 146 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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