NRG1

Protein identityUniProt · HPA

UniProt accession

Q02297

Gene

NRG1

Ensembl

ENSG00000157168

Chromosome

8

Canonical length

640 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Nucleoplasm

Secretome location

Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016]

Canonical amino-acid sequenceUniProt

640 residues, UniProt reviewed canonical sequence.

>Q02297|NRG1
     1  MSERKEGRGK GKGKKKERGS GKKPESAAGS QSPALPPRLK EMKSQESAAG SKLVLRCETS
    61  SEYSSLRFKW FKNGNELNRK NKPQNIKIQK KPGKSELRIN KASLADSGEY MCKVISKLGN
   121  DSASANITIV ESNEIITGMP ASTEGAYVSS ESPIRISVST EGANTSSSTS TSTTGTSHLV
   181  KCAEKEKTFC VNGGECFMVK DLSNPSRYLC KCQPGFTGAR CTENVPMKVQ NQEKAEELYQ
   241  KRVLTITGIC IALLVVGIMC VVAYCKTKKQ RKKLHDRLRQ SLRSERNNMM NIANGPHHPN
   301  PPPENVQLVN QYVSKNVISS EHIVEREAET SFSTSHYTST AHHSTTVTQT PSHSWSNGHT
   361  ESILSESHSV IVMSSVENSR HSSPTGGPRG RLNGTGGPRE CNSFLRHARE TPDSYRDSPH
   421  SERYVSAMTT PARMSPVDFH TPSSPKSPPS EMSPPVSSMT VSMPSMAVSP FMEEERPLLL
   481  VTPPRLREKK FDHHPQQFSS FHHNPAHDSN SLPASPLRIV EDEEYETTQE YEPAQEPVKK
   541  LANSRRAKRT KPNGHIANRL EVDSNTSSQS SNSESETEDE RVGEDTPFLG IQNPLAASLE
   601  ATPAFRLADS RTNPAGRFST QEEIQARLSS VIANQDPIAV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NRG1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.62

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NRG1.

Disease | ImmuneIEDB

Conditions an epitope on NRG1 was assayed in.

• narcolepsy B cell
• multiple sclerosis B cell
• peripheral nervous system disease B cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.26

gnomAD pLI

1

gnomAD missense Z

0.64

DepMap mean gene effect

0.1

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of protein kinase B activity
• brain development
• cardiac muscle cell differentiation
• cardiac muscle cell myoblast differentiation
• cell communication
• cell differentiation
• cell population proliferation
• cell surface receptor protein tyrosine kinase signaling pathway
• endocardial cell differentiation
• ERBB signaling pathway
• ERBB2 signaling pathway
• ERBB2-ERBB3 signaling pathway
• ERBB2-ERBB4 signaling pathway
• ERBB4 signaling pathway
• ERBB4-ERBB4 signaling pathway
• intracellular signal transduction
• mammary gland development
• negative regulation of cardiac muscle cell apoptotic process
• negative regulation of DNA-templated transcription
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• negative regulation of secretion
• nervous system development
• neural crest cell development
• peripheral nervous system development
• positive regulation of cardiac muscle cell proliferation
• positive regulation of cell adhesion
• positive regulation of cell growth
• positive regulation of cell population proliferation
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of protein-containing complex assembly
• positive regulation of striated muscle cell differentiation
• regulation of postsynaptic neurotransmitter receptor internalization
• ventricular cardiac muscle cell differentiation
• ventricular trabecula myocardium morphogenesis
• wound healing
• ERBB3 signaling pathway
• positive regulation of peptidyl-tyrosine autophosphorylation

Molecular functions

• chemorepellent activity
• cytokine activity
• ErbB-3 class receptor binding
• growth factor activity
• integrin binding
• nickel cation binding
• protein tyrosine kinase activator activity
• receptor ligand activity
• receptor tyrosine kinase binding
• signaling receptor binding
• transcription coregulator activity
• transmembrane receptor protein tyrosine kinase activator activity
• zinc ion binding

Cellular components

• apical plasma membrane
• extracellular region
• extracellular space
• glutamatergic synapse
• membrane
• nucleoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-like domain
• Neuregulin, C-terminal
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• Neuregulin
• EGF-like domain
• Neuregulin intracellular region
• Immunoglobulin I-set domain
• Neuregulin-1

KeywordsUniProt

• Cell membrane
• Chromosomal rearrangement
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Growth factor
• Immunoglobulin domain
• Membrane
• Nucleus
• Secreted
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NRG1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BACE1
• NRDC
• EGFR