UniProtKB - Q02297 (NRG1_HUMAN)
Protein
Pro-neuregulin-1, membrane-bound isoform
Gene
NRG1
Organism
Homo sapiens (Human)
Status
Functioni
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. Binds to ERBB4 (PubMed:10867024, PubMed:7902537). Binds to ERBB3 (PubMed:20682778). Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:20682778). Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (By similarity).By similarity4 Publications
GO - Molecular functioni
- chemorepellent activity Source: GO_Central
- cytokine activity Source: BHF-UCL
- ErbB-2 class receptor binding Source: Ensembl
- ErbB-3 class receptor binding Source: BHF-UCL
- growth factor activity Source: BHF-UCL
- integrin binding Source: UniProtKB
- protein tyrosine kinase activator activity Source: BHF-UCL
- receptor tyrosine kinase binding Source: UniProtKB
- signaling receptor binding Source: BHF-UCL
- transcription coregulator activity Source: MGI
- transmembrane receptor protein tyrosine kinase activator activity Source: UniProtKB
GO - Biological processi
- activation of MAPK activity Source: UniProtKB
- activation of protein kinase B activity Source: UniProtKB
- activation of transmembrane receptor protein tyrosine kinase activity Source: BHF-UCL
- animal organ development Source: GO_Central
- cardiac conduction system development Source: Ensembl
- cardiac muscle cell differentiation Source: BHF-UCL
- cardiac muscle cell myoblast differentiation Source: BHF-UCL
- cell communication Source: BHF-UCL
- cell differentiation Source: GO_Central
- cell morphogenesis Source: Ensembl
- cell population proliferation Source: BHF-UCL
- cellular protein complex disassembly Source: MGI
- chemorepulsion involved in interneuron migration from the subpallium to the cortex Source: Ensembl
- endocardial cell differentiation Source: BHF-UCL
- ERBB2 signaling pathway Source: Reactome
- ERBB3 signaling pathway Source: CAFA
- ERBB4 signaling pathway Source: UniProtKB
- ERBB signaling pathway Source: BHF-UCL
- glial cell fate commitment Source: Ensembl
- intracellular signal transduction Source: GO_Central
- locomotory behavior Source: Ensembl
- mammary gland development Source: BHF-UCL
- MAPK cascade Source: Reactome
- myelination in peripheral nervous system Source: Ensembl
- negative regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
- negative regulation of neuron migration Source: Ensembl
- negative regulation of protein catabolic process Source: Ensembl
- negative regulation of secretion Source: BHF-UCL
- negative regulation of transcription, DNA-templated Source: MGI
- nervous system development Source: GO_Central
- neural crest cell development Source: BHF-UCL
- neuron fate commitment Source: Ensembl
- neurotransmitter receptor metabolic process Source: Ensembl
- oligodendrocyte differentiation Source: Ensembl
- positive regulation of calcineurin-NFAT signaling cascade Source: Ensembl
- positive regulation of cardiac muscle cell differentiation Source: Ensembl
- positive regulation of cardiac muscle cell proliferation Source: BHF-UCL
- positive regulation of cell adhesion Source: BHF-UCL
- positive regulation of cell growth Source: BHF-UCL
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of gene expression Source: Ensembl
- positive regulation of peptidyl-tyrosine autophosphorylation Source: UniProtKB
- positive regulation of protein-containing complex assembly Source: BHF-UCL
- positive regulation of protein kinase B signaling Source: Reactome
- positive regulation of Ras protein signal transduction Source: Ensembl
- positive regulation of striated muscle cell differentiation Source: BHF-UCL
- postsynapse to nucleus signaling pathway Source: Ensembl
- regulation of cell motility Source: Reactome
- regulation of postsynaptic neurotransmitter receptor internalization Source: SynGO
- synapse assembly Source: Ensembl
- synaptic membrane adhesion Source: SynGO
- transmembrane receptor protein tyrosine kinase signaling pathway Source: BHF-UCL
- ventricular cardiac muscle cell differentiation Source: BHF-UCL
- ventricular trabecula myocardium morphogenesis Source: BHF-UCL
- wound healing Source: BHF-UCL
Keywordsi
| Molecular function | Growth factor |
Enzyme and pathway databases
| PathwayCommonsi | Q02297 |
| Reactomei | R-HSA-1227986, Signaling by ERBB2 [Q02297-10] R-HSA-1236394, Signaling by ERBB4 [Q02297-10] R-HSA-1250196, SHC1 events in ERBB2 signaling [Q02297-10] R-HSA-1250342, PI3K events in ERBB4 signaling R-HSA-1250347, SHC1 events in ERBB4 signaling R-HSA-1251985, Nuclear signaling by ERBB4 R-HSA-1257604, PIP3 activates AKT signaling [Q02297-10] R-HSA-1306955, GRB7 events in ERBB2 signaling [Q02297-10] R-HSA-1358803, Downregulation of ERBB2:ERBB3 signaling [Q02297-10] R-HSA-1963640, GRB2 events in ERBB2 signaling R-HSA-1963642, PI3K events in ERBB2 signaling [Q02297-10] R-HSA-2219530, Constitutive Signaling by Aberrant PI3K in Cancer [Q02297-10] R-HSA-5673001, RAF/MAP kinase cascade [Q02297-10] R-HSA-6785631, ERBB2 Regulates Cell Motility [Q02297-10] R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling [Q02297-10] R-HSA-8847993, ERBB2 Activates PTK6 Signaling [Q02297-10] R-HSA-8863795, Downregulation of ERBB2 signaling [Q02297-10] R-HSA-9620244, Long-term potentiation R-HSA-9664565, Signaling by ERBB2 KD Mutants [Q02297-10] R-HSA-9665686, Signaling by ERBB2 TMD/JMD mutants [Q02297-10] |
| SignaLinki | Q02297 |
| SIGNORi | Q02297 |
Names & Taxonomyi
| Protein namesi | Recommended name: Pro-neuregulin-1, membrane-bound isoformShort name: Pro-NRG1 Cleaved into the following chain: Alternative name(s): Acetylcholine receptor-inducing activity Short name: ARIA Breast cancer cell differentiation factor p45 Glial growth factor Heregulin Short name: HRG Neu differentiation factor Sensory and motor neuron-derived factor |
| Gene namesi | Name:NRG1 Synonyms:GGF, HGL, HRGA, NDF, SMDF |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000157168.18 |
| HGNCi | HGNC:7997, NRG1 |
| MIMi | 142445, gene |
| neXtProti | NX_Q02297 |
Subcellular locationi
Plasma membrane
Note: Does not seem to be active.
Extracellular region or secreted
Nucleus
Note: May be nuclear.
Extracellular region or secreted
Note: Has a signal peptide.
Other locations
Note: May possess an internal uncleaved signal sequence.
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: BHF-UCL
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- apical plasma membrane Source: BHF-UCL
- integral component of plasma membrane Source: Ensembl
- integral component of postsynaptic density membrane Source: SynGO
- integral component of presynaptic active zone membrane Source: SynGO
Other locations
- axon Source: Ensembl
- cytoplasm Source: Ensembl
- GABA-ergic synapse Source: Ensembl
- glutamatergic synapse Source: SynGO
- membrane Source: UniProtKB
- neuromuscular junction Source: Ensembl
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Topological domaini | 20 – 242 | ExtracellularSequence analysisAdd BLAST | 223 | |
| Transmembranei | 243 – 265 | Helical; Note=Internal signal sequenceSequence analysisAdd BLAST | 23 | |
| Topological domaini | 266 – 640 | CytoplasmicSequence analysisAdd BLAST | 375 |
Keywords - Cellular componenti
Cell membrane, Membrane, Nucleus, SecretedPathology & Biotechi
Involvement in diseasei
A chromosomal aberration involving NRG1 produces gamma-heregulin. Translocation t(8;11) with TENM4. The translocation fuses the 5'-end of TENM4 to NRG1 (isoform 8). The product of this translocation was first thought to be an alternatively spliced isoform. Gamma-heregulin is a soluble activating ligand for the ERBB2-ERBB3 receptor complex and acts as an autocrine growth factor in a specific breast cancer cell line (MDA-MB-175). Not detected in breast carcinoma samples, including ductal, lobular, medullary, and mucinous histological types, neither in other breast cancer cell lines.
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 181 | K → E: Defective in integrin-binding and in inducing ERBB3 phosphorylation; when associated with or without E-185 or E-187. No effect on ERBB3-binding, defective in integrin-binding and in ternary complex formation with ERBB3 and integrins, and defective in inducing NRG1-ERBB signaling; when associated with E-185 and E-187. 1 Publication | 1 | |
| Mutagenesisi | 185 | K → E: Defective in integrin-binding and in inducing ERBB3 phosphorylation; when associated with or without E-181 or E-187. No effect on ERBB3-binding, defective in integrin-binding and in ternary complex formation with ERBB3 and integrins, and defective in inducing NRG1-ERBB signaling; when associated with E-181 and E-187. 1 Publication | 1 | |
| Mutagenesisi | 187 | K → E: Defective in integrin-binding and in inducing ERBB3 phosphorylation; when associated with or without E-181 or E-185. No effect on ERBB3-binding, defective in integrin-binding and in ternary complex formation with ERBB3 and integrins, and defective in inducing NRG1-ERBB signaling; when associated with E-181 and E-185. 1 Publication | 1 |
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 34 | Breakpoint for translocation to form gamma-heregulin | 1 |
Organism-specific databases
| DisGeNETi | 3084 |
| MalaCardsi | NRG1 |
| OpenTargetsi | ENSG00000157168 |
| PharmGKBi | PA31776 |
Miscellaneous databases
| Pharosi | Q02297, Tbio |
Polymorphism and mutation databases
| BioMutai | NRG1 |
| DMDMi | 9297018 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| PropeptideiPRO_0000019462 | 1 – 19 | 1 PublicationAdd BLAST | 19 | |
| ChainiPRO_0000019463 | 20 – 640 | Pro-neuregulin-1, membrane-bound isoformAdd BLAST | 621 | |
| ChainiPRO_0000019464 | 20 – 241 | Neuregulin-1Add BLAST | 222 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Disulfide bondi | 57 ↔ 112 | By similarity | ||
| Glycosylationi | 120 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 126 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 164 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 182 ↔ 196 | 1 Publication | ||
| Disulfide bondi | 190 ↔ 210 | 1 Publication | ||
| Disulfide bondi | 212 ↔ 221 | 1 Publication |
Post-translational modificationi
Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.
N- and O-glycosylated. Extensive glycosylation precedes the proteolytic cleavage (By similarity).By similarity
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
| jPOSTi | Q02297 |
| MassIVEi | Q02297 |
| MaxQBi | Q02297 |
| PaxDbi | Q02297 |
| PeptideAtlasi | Q02297 |
| PRIDEi | Q02297 |
| ProteomicsDBi | 20533 58070 [Q02297-1] 58071 [Q02297-10] 58072 [Q02297-11] 58073 [Q02297-2] 58074 [Q02297-3] 58075 [Q02297-4] 58076 [Q02297-6] 58077 [Q02297-7] 58078 [Q02297-8] 58079 [Q02297-9] |
PTM databases
| GlyGeni | Q02297, 3 sites |
| iPTMneti | Q02297 |
| PhosphoSitePlusi | Q02297 |
Expressioni
Tissue specificityi
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.1 Publication
Developmental stagei
Detectable at early embryonic ages. Isoform 10 is highly expressed in developing spinal motor neurons and in developing cranial nerve nuclei. Expression is maintained only in both adult motor neurons and dorsal root ganglion neurons. Type IV isoforms are expressed in fetal brain.1 Publication
Gene expression databases
| Bgeei | ENSG00000157168, Expressed in ventricular zone and 174 other tissues |
| ExpressionAtlasi | Q02297, baseline and differential |
| Genevisiblei | Q02297, HS |
Organism-specific databases
| HPAi | ENSG00000157168, Tissue enhanced (brain) |
Interactioni
Subunit structurei
The cytoplasmic domain interacts with the LIM domain region of LIMK1 (By similarity).
Forms a ternary complex with ERBB3 and ITGAV:ITGB3 or ITGA6:ITGB4 (PubMed:20682778).
By similarity1 PublicationBinary interactionsi
Hide detailsIsoform 6 [Q02297-6]
| With | #Exp. | IntAct |
|---|---|---|
| ERBB3 [P21860] | 2 | EBI-15651799,EBI-720706 |
| ERBB4 [Q15303] | 3 | EBI-15651799,EBI-80371 |
Isoform 7 [Q02297-7]
| With | #Exp. | IntAct |
|---|---|---|
| ERBB2 [P04626] | 2 | EBI-2460927,EBI-641062 |
| ERBB3 [P21860] | 3 | EBI-2460927,EBI-720706 |
Isoform 10 [Q02297-10]
GO - Molecular functioni
- chemorepellent activity Source: GO_Central
- cytokine activity Source: BHF-UCL
- ErbB-2 class receptor binding Source: Ensembl
- ErbB-3 class receptor binding Source: BHF-UCL
- growth factor activity Source: BHF-UCL
- integrin binding Source: UniProtKB
- receptor tyrosine kinase binding Source: UniProtKB
- signaling receptor binding Source: BHF-UCL
Protein-protein interaction databases
| BioGRIDi | 109332, 73 interactors |
| CORUMi | Q02297 |
| DIPi | DIP-355N |
| IntActi | Q02297, 51 interactors |
| MINTi | Q02297 |
| STRINGi | 9606.ENSP00000384620 |
Miscellaneous databases
| RNActi | Q02297, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| SMRi | Q02297 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | Q02297 |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 37 – 128 | Ig-like C2-typeAdd BLAST | 92 | |
| Domaini | 178 – 222 | EGF-likePROSITE-ProRule annotationAdd BLAST | 45 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 165 – 177 | Ser/Thr-richAdd BLAST | 13 |
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.
Sequence similaritiesi
Belongs to the neuregulin family.Curated
Keywords - Domaini
EGF-like domain, Immunoglobulin domain, Transmembrane, Transmembrane helixPhylogenomic databases
| eggNOGi | ENOG502QRUM, Eukaryota |
| GeneTreei | ENSGT00940000157326 |
| HOGENOMi | CLU_023628_1_0_1 |
| InParanoidi | Q02297 |
| KOi | K05455 |
| OrthoDBi | 313400at2759 |
| PhylomeDBi | Q02297 |
| TreeFami | TF332469 |
Family and domain databases
| DisProti | DP01520 [Q02297-10] |
| Gene3Di | 2.60.40.10, 1 hit |
| InterProi | View protein in InterPro IPR013032, EGF-like_CS IPR000742, EGF-like_dom IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR013098, Ig_I-set IPR003599, Ig_sub IPR003598, Ig_sub2 IPR040180, Neuregulin IPR002154, Neuregulin_C IPR018250, NRG1 |
| PANTHERi | PTHR11100, PTHR11100, 1 hit PTHR11100:SF7, PTHR11100:SF7, 1 hit |
| Pfami | View protein in Pfam PF00008, EGF, 1 hit PF07679, I-set, 1 hit PF02158, Neuregulin, 1 hit |
| PRINTSi | PR01089, NEUREGULIN |
| SMARTi | View protein in SMART SM00181, EGF, 1 hit SM00409, IG, 1 hit SM00408, IGc2, 1 hit |
| SUPFAMi | SSF48726, SSF48726, 1 hit |
| PROSITEi | View protein in PROSITE PS00022, EGF_1, 1 hit PS01186, EGF_2, 1 hit PS50026, EGF_3, 1 hit PS50835, IG_LIKE, 1 hit |
Sequences (11+)i
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 11 isoformsi produced by alternative splicing. AlignAdd to basketNote: Additional isoforms seem to exist. Isoforms have been classified as type I NRGs (isoforms with an Ig domain and a glycosylation domain, isoforms 1-8), type II NRGs (isoforms with an Ig domain but no glycosylation domain, isoform 9), type III NRGs (isoforms with a Cys-rich domain, isoform 10) and type IV NRGs (isoforms with additional 5' exons, isoform 11). All these isoforms perform distinct tissue-specific functions.
This entry has 11 described isoforms and 21 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q02297-1) [UniParc]FASTAAdd to basket
Also known as: Alpha
This isoform has been chosen as the canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MSERKEGRGK GKGKKKERGS GKKPESAAGS QSPALPPRLK EMKSQESAAG
60 70 80 90 100
SKLVLRCETS SEYSSLRFKW FKNGNELNRK NKPQNIKIQK KPGKSELRIN
110 120 130 140 150
KASLADSGEY MCKVISKLGN DSASANITIV ESNEIITGMP ASTEGAYVSS
160 170 180 190 200
ESPIRISVST EGANTSSSTS TSTTGTSHLV KCAEKEKTFC VNGGECFMVK
210 220 230 240 250
DLSNPSRYLC KCQPGFTGAR CTENVPMKVQ NQEKAEELYQ KRVLTITGIC
260 270 280 290 300
IALLVVGIMC VVAYCKTKKQ RKKLHDRLRQ SLRSERNNMM NIANGPHHPN
310 320 330 340 350
PPPENVQLVN QYVSKNVISS EHIVEREAET SFSTSHYTST AHHSTTVTQT
360 370 380 390 400
PSHSWSNGHT ESILSESHSV IVMSSVENSR HSSPTGGPRG RLNGTGGPRE
410 420 430 440 450
CNSFLRHARE TPDSYRDSPH SERYVSAMTT PARMSPVDFH TPSSPKSPPS
460 470 480 490 500
EMSPPVSSMT VSMPSMAVSP FMEEERPLLL VTPPRLREKK FDHHPQQFSS
510 520 530 540 550
FHHNPAHDSN SLPASPLRIV EDEEYETTQE YEPAQEPVKK LANSRRAKRT
560 570 580 590 600
KPNGHIANRL EVDSNTSSQS SNSESETEDE RVGEDTPFLG IQNPLAASLE
610 620 630 640
ATPAFRLADS RTNPAGRFST QEEIQARLSS VIANQDPIAV
Isoform 9 (identifier: Q02297-9) [UniParc]FASTAAdd to basket
Also known as: GGF2, GGFHPP2
The sequence of this isoform differs from the canonical sequence as follows:
1-33: MSERKEGRGKGKGKKKERGSGKKPESAAGSQSP → MRWRRAPRRS...EVSRVLCKRC
134-168: EIITGMPASTEGAYVSSESPIRISVSTEGANTSSS → A
213-241: QPGFTGARCTENVPMKVQNQEKAEELYQK → PNEFTGDRCQNYVMASFYSTSTPFLSLPE
242-640: Missing.
Isoform 10 (identifier: Q02297-10) [UniParc]FASTAAdd to basket
Also known as: SMDF
The sequence of this isoform differs from the canonical sequence as follows:
1-166: Missing.
167-167: S → MEIYSPDMSE...ETNLQTAPKL
213-241: QPGFTGARCTENVPMKVQNQEKAEELYQK → PNEFTGDRCQNYVMASFYSTSTPFLSLPE
242-640: Missing.
Note: Potential internal signal sequence at positions 76-100.Curated
Show »Isoform 11 (identifier: Q02297-11) [UniParc]FASTAAdd to basket
Also known as: Type IV-beta1a
The sequence of this isoform differs from the canonical sequence as follows:
1-21: Missing.
22-33: KKPESAAGSQSP → MGKGRAGRVGTT
134-168: EIITGMPASTEGAYVSSESPIRISVSTEGANTSSS → A
213-234: QPGFTGARCTENVPMKVQNQEK → PNEFTGDRCQNYVMASFYKHLGIEFME
Isoform 12 (identifier: Q02297-12) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
213-233: QPGFTGARCTENVPMKVQNQE → PNEFTGDRCQNYVMASFY
424-640: Missing.
Computationally mapped potential isoform sequencesi
There are 21 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| H0YBA3 | H0YBA3_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 713 | Annotation score: | ||
| A0A494C0K4 | A0A494C0K4_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 459 | Annotation score: | ||
| A0A494C1F5 | A0A494C1F5_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 624 | Annotation score: | ||
| A0A494C1F8 | A0A494C1F8_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 607 | Annotation score: | ||
| A0A494C043 | A0A494C043_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 461 | Annotation score: | ||
| F6RJN6 | F6RJN6_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 308 | Annotation score: | ||
| A0A494C0L9 | A0A494C0L9_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 522 | Annotation score: | ||
| A0A494C0Q4 | A0A494C0Q4_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 700 | Annotation score: | ||
| A0A494C1B5 | A0A494C1B5_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 483 | Annotation score: | ||
| A0A5F9ZHA5 | A0A5F9ZHA5_HUMAN | Pro-neuregulin-1, membrane-bound is... | NRG1 | 168 | Annotation score: | ||
| There are more potential isoformsShow all | |||||||
Sequence cautioni
The sequence AAA19955 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence AAC51756 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 94 | K → A in AAA19953 (PubMed:7509448).Curated | 1 | |
| Sequence conflicti | 107 | S → P in ABQ53539 (PubMed:17565985).Curated | 1 | |
| Sequence conflicti | 261 | V → L in ABQ53540 (PubMed:17565985).Curated | 1 | |
| Sequence conflicti | 414 | S → F in AAA19953 (PubMed:7509448).Curated | 1 | |
| Sequence conflicti | 535 | Q → R in AAA19951 (PubMed:7509448).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
|---|---|---|---|---|---|
| Natural variantiVAR_009307 | 38 | R → Q1 PublicationCorresponds to variant dbSNP:rs3924999Ensembl. | 1 | ||
| Natural variantiVAR_053531 | 289 | M → T2 PublicationsCorresponds to variant dbSNP:rs10503929Ensembl. | 1 | ||
| Natural variantiVAR_009308 | 463 | M → K. | 1 | ||
| Isoform 10 (identifier: Q02297-10) | |||||
| Natural variantiVAR_082866 | 46 | G → RCuratedCorresponds to variant dbSNP:rs3735774Ensembl. | 1 | ||
| Natural variantiVAR_082867 | 127 | A → PCuratedCorresponds to variant dbSNP:rs34822181Ensembl. | 1 | ||
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_037562 | 1 – 166 | Missing in isoform 10. 3 PublicationsAdd BLAST | 166 | |
| Alternative sequenceiVSP_003425 | 1 – 33 | MSERK…GSQSP → MRWRRAPRRSGRPGPRAQRP GSAARSSPPLPLLPLLLLLG TAALAPGAAAGNEAAPAGAS VCYSSPPSVGSVQELAQRAA VVIEGKVHPQRRQQGALDRK AAAAAGEAGAWGGDREPPAA GPRALGPPAEEPLLAANGTV PSWPTAPVPSAGEPGEEAPY LVKVHQVWAVKAGGLKKDSL LTVRLGTWGHPAFPSCGRLK EDSRYIFFMEPDANSTSRAP AAFRASFPPLETGRNLKKEV SRVLCKRC in isoform 9. 1 PublicationAdd BLAST | 33 | |
| Alternative sequenceiVSP_037563 | 1 – 21 | Missing in isoform 11. 1 PublicationAdd BLAST | 21 | |
| Alternative sequenceiVSP_037564 | 22 – 33 | KKPES…GSQSP → MGKGRAGRVGTT in isoform 11. 1 PublicationAdd BLAST | 12 | |
| Alternative sequenceiVSP_003426 | 134 – 168 | EIITG…NTSSS → A in isoform 9 and isoform 11. 2 PublicationsAdd BLAST | 35 | |
| Alternative sequenceiVSP_037565 | 167 | S → MEIYSPDMSEVAAERSSSPS TQLSADPSLDGLPAAEDMPE PQTEDGRTPGLVGLAVPCCA CLEAERLRGCLNSEKICIVP ILACLVSLCLCIAGLKWVFV DKIFEYDSPTHLDPGGLGQD PIISLDATAASAVWVSSEAY TSPVSRAQSESEVQVTVQGD KAVVSFEPSAAPTPKNRIFA FSFLPSTAPSFPSPTRNPEV RTPKSATQPQTTETNLQTAP KL in isoform 10. 3 Publications | 1 | |
| Alternative sequenceiVSP_003429 | 213 – 241 | QPGFT…ELYQK → PNEFTGDRCQNYVMASFYST STPFLSLPE in isoform 8, isoform 9 and isoform 10. 6 PublicationsAdd BLAST | 29 | |
| Alternative sequenceiVSP_003428 | 213 – 234 | QPGFT…QNQEK → PNEFTGDRCQNYVMASFYKH LGIEFME in isoform 6 and isoform 11. 3 PublicationsAdd BLAST | 22 | |
| Alternative sequenceiVSP_003427 | 213 – 233 | QPGFT…VQNQE → PNEFTGDRCQNYVMASFY in isoform 7 and isoform 12. 3 PublicationsAdd BLAST | 21 | |
| Alternative sequenceiVSP_003432 | 234 – 247 | KAEEL…VLTIT → SAQMSLLVIAAKTT in isoform 4. 1 PublicationAdd BLAST | 14 | |
| Alternative sequenceiVSP_003431 | 234 | K → KHLGIEFIE in isoform 2. 1 Publication | 1 | |
| Alternative sequenceiVSP_003430 | 242 – 640 | Missing in isoform 8, isoform 9 and isoform 10. 6 PublicationsAdd BLAST | 399 | |
| Alternative sequenceiVSP_003433 | 248 – 640 | Missing in isoform 4. 1 PublicationAdd BLAST | 393 | |
| Alternative sequenceiVSP_046417 | 424 – 640 | Missing in isoform 12. 1 PublicationAdd BLAST | 217 | |
| Alternative sequenceiVSP_003434 | 424 – 462 | YVSAM…SMTVS → HNLIAELRRNKAHRSKCMQI QLSATHLRSSSIPHLGFIL in isoform 3. 1 PublicationAdd BLAST | 39 | |
| Alternative sequenceiVSP_003435 | 463 – 640 | Missing in isoform 3. 1 PublicationAdd BLAST | 178 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicing, Chromosomal rearrangement, PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
| Protein Spotlight Tipping the mind - Issue 129 of June 2011 |
Sequence databases
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1HAE | NMR | - | A | 177-239 | [»] | |
| 1HAF | NMR | - | A | 177-239 | [»] | |
| 1HRE | NMR | - | A | 175-241 | [»] | |
| 1HRF | NMR | - | A | 175-241 | [»] | |
| 3U7U | X-ray | 3.03 | G/H/I/J/K/L | 175-212 | [»] | |
| SMRi | Q02297 | |||||
| ModBasei | Search... | |||||
| PDBe-KBi | Search... | |||||
Protein-protein interaction databases
| BioGRIDi | 109332, 73 interactors |
| CORUMi | Q02297 |
| DIPi | DIP-355N |
| IntActi | Q02297, 51 interactors |
| MINTi | Q02297 |
| STRINGi | 9606.ENSP00000384620 |
PTM databases
| GlyGeni | Q02297, 3 sites |
| iPTMneti | Q02297 |
| PhosphoSitePlusi | Q02297 |
Polymorphism and mutation databases
| BioMutai | NRG1 |
| DMDMi | 9297018 |
Proteomic databases
| jPOSTi | Q02297 |
| MassIVEi | Q02297 |
| MaxQBi | Q02297 |
| PaxDbi | Q02297 |
| PeptideAtlasi | Q02297 |
| PRIDEi | Q02297 |
| ProteomicsDBi | 20533 58070 [Q02297-1] 58071 [Q02297-10] 58072 [Q02297-11] 58073 [Q02297-2] 58074 [Q02297-3] 58075 [Q02297-4] 58076 [Q02297-6] 58077 [Q02297-7] 58078 [Q02297-8] 58079 [Q02297-9] |
Protocols and materials databases
| Antibodypediai | 3706, 925 antibodies |
| DNASUi | 3084 |
Genome annotation databases
Organism-specific databases
| CTDi | 3084 |
| DisGeNETi | 3084 |
| EuPathDBi | HostDB:ENSG00000157168.18 |
| GeneCardsi | NRG1 |
| HGNCi | HGNC:7997, NRG1 |
| HPAi | ENSG00000157168, Tissue enhanced (brain) |
| MalaCardsi | NRG1 |
| MIMi | 142445, gene |
| neXtProti | NX_Q02297 |
| OpenTargetsi | ENSG00000157168 |
| PharmGKBi | PA31776 |
| GenAtlasi | Search... |
Phylogenomic databases
| eggNOGi | ENOG502QRUM, Eukaryota |
| GeneTreei | ENSGT00940000157326 |
| HOGENOMi | CLU_023628_1_0_1 |
| InParanoidi | Q02297 |
| KOi | K05455 |
| OrthoDBi | 313400at2759 |
| PhylomeDBi | Q02297 |
| TreeFami | TF332469 |
Enzyme and pathway databases
| PathwayCommonsi | Q02297 |
| Reactomei | R-HSA-1227986, Signaling by ERBB2 [Q02297-10] R-HSA-1236394, Signaling by ERBB4 [Q02297-10] R-HSA-1250196, SHC1 events in ERBB2 signaling [Q02297-10] R-HSA-1250342, PI3K events in ERBB4 signaling R-HSA-1250347, SHC1 events in ERBB4 signaling R-HSA-1251985, Nuclear signaling by ERBB4 R-HSA-1257604, PIP3 activates AKT signaling [Q02297-10] R-HSA-1306955, GRB7 events in ERBB2 signaling [Q02297-10] R-HSA-1358803, Downregulation of ERBB2:ERBB3 signaling [Q02297-10] R-HSA-1963640, GRB2 events in ERBB2 signaling R-HSA-1963642, PI3K events in ERBB2 signaling [Q02297-10] R-HSA-2219530, Constitutive Signaling by Aberrant PI3K in Cancer [Q02297-10] R-HSA-5673001, RAF/MAP kinase cascade [Q02297-10] R-HSA-6785631, ERBB2 Regulates Cell Motility [Q02297-10] R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling [Q02297-10] R-HSA-8847993, ERBB2 Activates PTK6 Signaling [Q02297-10] R-HSA-8863795, Downregulation of ERBB2 signaling [Q02297-10] R-HSA-9620244, Long-term potentiation R-HSA-9664565, Signaling by ERBB2 KD Mutants [Q02297-10] R-HSA-9665686, Signaling by ERBB2 TMD/JMD mutants [Q02297-10] |
| SignaLinki | Q02297 |
| SIGNORi | Q02297 |
Miscellaneous databases
| BioGRID-ORCSi | 3084, 3 hits in 884 CRISPR screens |
| ChiTaRSi | NRG1, human |
| EvolutionaryTracei | Q02297 |
| GeneWikii | Neuregulin_1 |
| GenomeRNAii | 3084 |
| Pharosi | Q02297, Tbio |
| PROi | PR:Q02297 |
| RNActi | Q02297, protein |
| SOURCEi | Search... |
Gene expression databases
| Bgeei | ENSG00000157168, Expressed in ventricular zone and 174 other tissues |
| ExpressionAtlasi | Q02297, baseline and differential |
| Genevisiblei | Q02297, HS |
Family and domain databases
| DisProti | DP01520 [Q02297-10] |
| Gene3Di | 2.60.40.10, 1 hit |
| InterProi | View protein in InterPro IPR013032, EGF-like_CS IPR000742, EGF-like_dom IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR013098, Ig_I-set IPR003599, Ig_sub IPR003598, Ig_sub2 IPR040180, Neuregulin IPR002154, Neuregulin_C IPR018250, NRG1 |
| PANTHERi | PTHR11100, PTHR11100, 1 hit PTHR11100:SF7, PTHR11100:SF7, 1 hit |
| Pfami | View protein in Pfam PF00008, EGF, 1 hit PF07679, I-set, 1 hit PF02158, Neuregulin, 1 hit |
| PRINTSi | PR01089, NEUREGULIN |
| SMARTi | View protein in SMART SM00181, EGF, 1 hit SM00409, IG, 1 hit SM00408, IGc2, 1 hit |
| SUPFAMi | SSF48726, SSF48726, 1 hit |
| PROSITEi | View protein in PROSITE PS00022, EGF_1, 1 hit PS01186, EGF_2, 1 hit PS50026, EGF_3, 1 hit PS50835, IG_LIKE, 1 hit |
| ProtoNeti | Search... |
| MobiDBi | Search... |
Entry informationi
| Entry namei | NRG1_HUMAN | |
| Accessioni | Q02297Primary (citable) accession number: Q02297 Secondary accession number(s): A5YAK4 Q9UPE3 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
| Last sequence update: | January 23, 2007 | |
| Last modified: | August 12, 2020 | |
| This is version 229 of the entry and version 3 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any 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
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM
Main funding by:
National Institutes of Health
The European Molecular Biology Laboratory
State Secretariat for Education, Research and InnovationSERI
The European Molecular Biology LaboratoryState Secretariat for Education, Research and InnovationSERIWe'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
Do not show this banner again