Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage Cell Signaling Technology
PhosphoSitePlus
HomeAbout PhosphoSiteUsing PhosphoSiteCuration ProcessContact
NIH-logos NIGMS Logo NIAAA Logo NCI Logo NIH Logo
Protein Page:
NRG1 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
NRG1 Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. The cytoplasmic domain interacts with the LIM domain region of LIMK1. Interacts with ERBB3 and ERBB4. Type I isoforms are the predominant forms expressed in the endocardium. Isoform alpha is expressed in breast, ovary, testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, salivary gland, small intestine and brain, but not in uterus, stomach, pancreas, and spleen. Isoform 3 is the predominant form in mesenchymal cells and in non-neuronal organs, whereas isoform 6 is the major neuronal form. Isoform 8 is expressed in spinal cord and brain. Isoform 9 is the major form in skeletal muscle cells; in the nervous system it is expressed in spinal cord and brain. Also detected in adult heart, placenta, lung, liver, kidney, and pancreas. Isoform 10 is expressed in nervous system: spinal cord motor neurons, dorsal root ganglion neurons, and brain. Predominant isoform expressed in sensory and motor neurons. Not detected in adult heart, placenta, lung, liver, skeletal muscle, kidney, and pancreas. Not expressed in fetal lung, liver and kidney. Type IV isoforms are brain-specific. Belongs to the neuregulin family. 10 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Cytokine; Motility/polarity/chemotaxis; Ligand, receptor tyrosine kinase; Cell development/differentiation; Membrane protein, integral
Cellular Component: extracellular space; membrane; integral to plasma membrane; axon; cytoplasm; apical plasma membrane; extracellular region; neuromuscular junction; nucleus
Molecular Function: ErbB-2 class receptor binding; protein binding; transmembrane receptor protein tyrosine kinase activator activity; ErbB-3 class receptor binding; growth factor activity; cytokine activity; transcription cofactor activity; protein tyrosine kinase activator activity; receptor tyrosine kinase binding; receptor binding
Biological Process: regulation of protein heterodimerization activity; transmembrane receptor protein tyrosine kinase activation (dimerization); positive regulation of cell adhesion; neural crest cell development; cellular protein complex disassembly; wound healing; nerve growth factor receptor signaling pathway; cell morphogenesis; ventricular cardiac muscle cell differentiation; locomotory behavior; positive regulation of striated muscle cell differentiation; cardiac muscle cell differentiation; synaptogenesis; mammary gland development; cell communication; positive regulation of cardiac muscle cell proliferation; epidermal growth factor receptor signaling pathway; nervous system development; cell migration; fibroblast growth factor receptor signaling pathway; phosphoinositide-mediated signaling; neurotransmitter receptor metabolic process; regulation of protein homodimerization activity; neuron fate commitment; MAPKKK cascade; positive regulation of cell growth; peripheral nervous system development; positive regulation of protein kinase B signaling cascade; cell proliferation; embryonic development; glial cell fate commitment; innate immune response; negative regulation of secretion; positive regulation of Ras protein signal transduction; negative regulation of protein catabolic process; negative regulation of transcription, DNA-dependent; transmembrane receptor protein tyrosine kinase signaling pathway
Reference #:  Q02297 (UniProtKB)
Alt. Names/Synonyms: Acetylcholine receptor-inducing activity; ARIA; Breast cancer cell differentiation factor p45; GGF; GGF2; Glial growth factor; Heregulin; heregulin, alpha (45kD, ERBB2 p185-activator); HGL; HRG; HRG1; HRGA; NDF; Neu differentiation factor; neuregulin 1; Neuregulin-1; NRG1; Pro-neuregulin-1, membrane-bound isoform; Pro-NRG1; sensory and motor neuron derived factor; Sensory and motor neuron-derived factor; SMDF
Gene Symbols: NRG1
Molecular weight: 70,392 Da
Basal Isoelectric point: Predict pI for various phosphorylation states
CST Pathways:  ErbB/HER Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

NRG1

Protein Structure Not Found.


STRING  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  DISEASE  |  Scansite  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene  |  InnateDB


Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 4 K10-ac ERKEGRGkGkGKkkE
0 3 K12-ac KEGRGkGkGKkkERG
0 2 K14 GRGkGkGKkkERGSG
0 2 K15-ac RGkGkGKkkERGSGK
0 1 K16-ac GkGkGKkkERGSGKK
0 1 K43-ac PPRLKEMkSQESAAG
0 1 S166 STEGANTSSStsTST
0 1 S167 TEGANTSSStsTSTT
0 1 S168 EGANTSSStsTSTTG
0 1 T169-p GANTSSStsTSTTGT
0 1 S170-p ANTSSStsTSTTGTS
0 1 - gap
0 1 T171 NTSSStsTSTTGTSH
0 1 S172 TSSStsTSTTGTSHL
0 1 T173 SSStsTSTTGTSHLV
0 1 T174 SStsTSTTGTSHLVK
0 1 T176 tsTSTTGTSHLVKCA
0 2 S177 sTSTTGTSHLVKCAE
1 0 S281-p LHDRLRQsLRSERNN
0 1 S414-p HARETPDsyRDSPHS
0 1 Y415-p ARETPDsyRDSPHSE
0 1 Y424-p DSPHSERyVSAMTTP
0 3 S435-p MTTPARMsPVDFHTP
0 3 Y525-p RIVEDEEyETtQEyE
0 1 T528-p EDEEyETtQEyEPAQ
0 3 Y531-p EyETtQEyEPAQEPV
0 1 K551-ac SRRAKRTkPNGHIAN
  NRG1 iso6  
K10 ERKEGRGKGKGKKKE
K12 KEGRGKGKGKKKERG
K14 GRGKGKGKKKERGSG
K15 RGKGKGKKKERGSGK
K16 GKGKGKKKERGSGKK
K43 PPRLKEMKSQESAAG
S166 STEGANTSSSTSTST
S167 TEGANTSSSTSTSTT
S168 EGANTSSSTSTSTTG
T169 GANTSSSTSTSTTGT
S170 ANTSSSTSTSTTGTS
- gap
T171 NTSSSTSTSTTGTSH
S172 TSSSTSTSTTGTSHL
T173 SSSTSTSTTGTSHLV
T174 SSTSTSTTGTSHLVK
T176 TSTSTTGTSHLVKCA
S177 STSTTGTSHLVKCAE
S286-p LHDRLRQsLRSERNN
S419 HARETPDSYRDSPHS
Y420 ARETPDSYRDSPHSE
Y429 DSPHSERYVSAMTTP
S440 MTTPARMSPVDFHTP
Y530 RIVEDEEYETTQEYE
T533 EDEEYETTQEYEPAQ
Y536 EYETTQEYEPAQEPV
K556 SRRAKRTKPNGHIAN
  NRG1 iso9  
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
S203-p CGRLKEDsRYIFFME
T352 VESNATSTSTTGTSH
S353 ESNATSTSTTGTSHL
T354 SNATSTSTTGTSHLV
T355 NATSTSTTGTSHLVK
T357 TSTSTTGTSHLVKCA
S358 STSTTGTSHLVKCAE
- gap
- under review  
- under review  
- gap
- gap
- gap
- gap
- gap
- gap
  NRG1 iso12  
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
T15 SIEDITATSTSTTGT
S16 IEDITATSTSTTGTs
- gap
T17 EDITATSTSTTGTsH
S18 DITATSTSTTGTsHL
T19 ITATSTSTTGTsHLV
T20 TATSTSTTGTsHLVK
T22 TSTSTTGTsHLVKCA
S23-p STSTTGTsHLVKCAE
S127 LHDRLRQSLRSERNN
S260 HARETPDSYRDSPHS
Y261 ARETPDSYRDSPHSE
- gap
- gap
- gap
- gap
- gap
- gap
  mouse

 
K10-ac ERKEGRGkGkGkKKD
K12-ac KEGRGkGkGkKKDRG
K14-ac GRGkGkGkKKDRGSR
K15 RGkGkGkKKDRGSRG
K16 GkGkGkKKDRGSRGK
K43 PPRLKEMKSQESAAG
S166 STEGANTSSSTSTST
S167 TEGANTSSSTSTSTT
S168 EGANTSSSTSTSTTG
T169 GANTSSSTSTSTTGT
S170 ANTSSSTSTSTTGTS
- gap
T171 NTSSSTSTSTTGTSH
S172 TSSSTSTSTTGTSHL
T173 SSSTSTSTTGTSHLI
T174 SSTSTSTTGTSHLIK
T176 TSTSTTGTSHLIKCA
S177 STSTTGTSHLIKCAE
S286 LHDRLRQSLRSERNN
S419 HARETPDSYRDSPHS
Y420 ARETPDSYRDSPHSE
Y429 DSPHSERYVSAMTTP
S440 MTTPARMSPVDFHTP
Y530 RIVEDEEYETTQEYE
T533 EDEEYETTQEYEPIQ
Y536 EYETTQEYEPIQEPI
K556 SRRAKRTKPNGHIAN
  rat

 
K10 ERKEGRGKGKGKKKD
K12 KEGRGKGKGKKKDRG
K14 GRGKGKGKKKDRGSR
K15 RGKGKGKKKDRGSRG
K16 GKGKGKKKDRGSRGK
K43 PPRLKEMKSQESAAG
S166-p STEGANTsssTStst
S167-p TEGANTsssTStstt
S168-p EGANTsssTStsttG
T169 GANTsssTStsttGt
S170 ANTsssTStsttGts
- gap
T171-p NTsssTStsttGtsH
S172-p TsssTStsttGtsHL
T173-p sssTStsttGtsHLI
T174-p ssTStsttGtsHLIK
T176-p TStsttGtsHLIKCA
S177-p StsttGtsHLIKCAE
S304 LHDRLRQSLRSERSN
S436 HARETPDSYRDSPHS
Y437 ARETPDSYRDSPHSE
Y446 DSPHSERYVSAMTTP
S457-p MTTPARMsPVDFHTP
Y547 RIVEDEEYETTQEYE
T550 EDEEYETTQEYESVQ
Y553 EYETTQEYESVQEPV
K573 SRRAKRTKPNGHIAN
Home  |  Curator Login With enhanced literature mining using Linguamatics I2E I2E Logo Produced by 3rd Millennium  |  Design by Digizyme
©2003-2013 Cell Signaling Technology, Inc.