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Q02297 (NRG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pro-neuregulin-1, membrane-bound isoform

Short name=Pro-NRG1

Cleaved into the following chain:

  1. Neuregulin-1
    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 names
Name:NRG1
Synonyms:GGF, HGL, HRGA, NDF, SMDF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length640 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.14 Ref.15

Subunit structure

The cytoplasmic domain interacts with the LIM domain region of LIMK1 By similarity. Interacts with ERBB3 and ERBB4. Ref.15 Ref.18

Subcellular location

Pro-neuregulin-1, membrane-bound isoform: Cell membrane; Single-pass type I membrane protein. Note: Does not seem to be active.

Neuregulin-1: Secreted.

Isoform 8: Nucleus. Note: May be nuclear.

Isoform 9: Secreted. Note: Has a signal peptide.

Isoform 10: Membrane; Single-pass type I membrane protein. Note: May possess an internal uncleaved signal sequence.

Tissue specificity

Type I isoforms are the predominant forms expressed in the endocardium. Isoform alphais 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 expressedin 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. Ref.10

Developmental stage

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. Ref.10

Domain

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.

Post-translational modification

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. Ref.14

Involvement in disease

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.

Sequence similarities

Belongs to the neuregulin family.

Contains 1 EGF-like domain.

Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Sequence caution

The sequence AAA19955.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

The sequence AAC51756.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Nucleus
Secreted
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DomainEGF-like domain
Immunoglobulin domain
Transmembrane
Transmembrane helix
   Molecular functionGrowth factor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

MAPK cascade

Inferred from electronic annotation. Source: Ensembl

cardiac conduction system development

Inferred from electronic annotation. Source: Ensembl

cardiac muscle cell myoblast differentiation

Inferred from direct assay PubMed 17336907. Source: BHF-UCL

cell migration

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Inferred from direct assay PubMed 11389077. Source: BHF-UCL

cellular protein complex disassembly

Inferred from genetic interaction PubMed 15155732. Source: MGI

embryo development

Inferred from electronic annotation. Source: InterPro

endocardial cell differentiation

Inferred from direct assay PubMed 17336907. Source: BHF-UCL

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

glial cell fate commitment

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

mammary gland development

Traceable author statement PubMed 17432114. Source: BHF-UCL

negative regulation of cardiac muscle cell apoptotic process

Inferred from direct assay PubMed 9553078. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from direct assay PubMed 9553078. Source: BHF-UCL

negative regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of secretion

Inferred from direct assay PubMed 10559227. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15073182. Source: MGI

nervous system development

Traceable author statement PubMed 17432114. Source: BHF-UCL

neural crest cell development

Traceable author statement PubMed 17432114. Source: BHF-UCL

neuron fate commitment

Inferred from electronic annotation. Source: Ensembl

neurotransmitter receptor metabolic process

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peripheral nervous system development

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of Ras protein signal transduction

Inferred from electronic annotation. Source: Ensembl

positive regulation of cardiac muscle cell proliferation

Inferred from direct assay PubMed 9553078. Source: BHF-UCL

positive regulation of cell adhesion

Inferred from direct assay PubMed 7556068. Source: BHF-UCL

positive regulation of cell growth

Inferred from direct assay PubMed 9553078. Source: BHF-UCL

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of striated muscle cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of protein heterodimerization activity

Inferred from direct assay PubMed 10559227. Source: BHF-UCL

regulation of protein homodimerization activity

Traceable author statement PubMed 16412517. Source: BHF-UCL

synapse assembly

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein tyrosine kinase signaling pathway

Inferred from direct assay PubMed 7514177. Source: BHF-UCL

ventricular cardiac muscle cell differentiation

Inferred from direct assay PubMed 9553078. Source: BHF-UCL

ventricular trabecula myocardium morphogenesis

Inferred from direct assay PubMed 17336907. Source: BHF-UCL

wound healing

Inferred from direct assay PubMed 12646923. Source: BHF-UCL

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 12646923. Source: BHF-UCL

axon

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular region

Non-traceable author statement Ref.14Ref.1Ref.3. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 11389077PubMed 12646923PubMed 11389077. Source: BHF-UCL

integral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

membrane

Non-traceable author statement Ref.3. Source: UniProtKB

neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionErbB-3 class receptor binding

Inferred from direct assay PubMed 7556068. Source: BHF-UCL

cytokine activity

Traceable author statement PubMed 10372964. Source: BHF-UCL

growth factor activity

Inferred from direct assay PubMed 11389077. Source: BHF-UCL

protein tyrosine kinase activator activity

Inferred from direct assay PubMed 7556068. Source: BHF-UCL

receptor tyrosine kinase binding

Non-traceable author statement Ref.14Ref.1. Source: UniProtKB

transcription cofactor activity

Inferred from direct assay PubMed 15073182. Source: MGI

transmembrane receptor protein tyrosine kinase activator activity

Inferred by curator PubMed 9553078. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 11 isoforms produced by alternative splicing. [Align] [Select]

Note: 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.
Isoform 1 (identifier: Q02297-1)

Also known as: Alpha;

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.
Isoform 2 (identifier: Q02297-2)

Also known as: Alpha1A;

The sequence of this isoform differs from the canonical sequence as follows:
     234-234: K → KHLGIEFIE
Isoform 3 (identifier: Q02297-3)

Also known as: Alpha2B;

The sequence of this isoform differs from the canonical sequence as follows:
     424-462: YVSAMTTPAR...SPPVSSMTVS → HNLIAELRRN...SSIPHLGFIL
     463-640: Missing.
Isoform 4 (identifier: Q02297-4)

Also known as: Alpha3;

The sequence of this isoform differs from the canonical sequence as follows:
     234-247: KAEELYQKRVLTIT → SAQMSLLVIAAKTT
     248-640: Missing.
Isoform 6 (identifier: Q02297-6)

Also known as: Beta1; Beta1A;

The sequence of this isoform differs from the canonical sequence as follows:
     213-234: QPGFTGARCTENVPMKVQNQEK → PNEFTGDRCQNYVMASFYKHLGIEFME
Isoform 7 (identifier: Q02297-7)

Also known as: Beta2;

The sequence of this isoform differs from the canonical sequence as follows:
     213-233: QPGFTGARCTENVPMKVQNQE → PNEFTGDRCQNYVMASFY
Isoform 8 (identifier: Q02297-8)

Also known as: Beta3; GGFHFB1;

The sequence of this isoform differs from the canonical sequence as follows:
     213-241: QPGFTGARCTENVPMKVQNQEKAEELYQK → PNEFTGDRCQNYVMASFYSTSTPFLSLPE
     242-640: Missing.
Isoform 9 (identifier: Q02297-9)

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)

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.
Isoform 11 (identifier: Q02297-11)

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)

The sequence of this isoform differs from the canonical sequence as follows:
     213-233: QPGFTGARCTENVPMKVQNQE → PNEFTGDRCQNYVMASFY
     424-640: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 1919
PRO_0000019462
Chain20 – 640621Pro-neuregulin-1, membrane-bound isoform
PRO_0000019463
Chain20 – 241222Neuregulin-1
PRO_0000019464

Regions

Topological domain20 – 242223Extracellular Potential
Transmembrane243 – 26523Helical; Note=Internal signal sequence; Potential
Topological domain266 – 640375Cytoplasmic Potential
Domain37 – 12892Ig-like C2-type
Domain178 – 22245EGF-like
Compositional bias165 – 17713Ser/Thr-rich

Sites

Site341Breakpoint for translocation to form gamma-heregulin

Amino acid modifications

Glycosylation1201N-linked (GlcNAc...) Potential
Glycosylation1261N-linked (GlcNAc...) Potential
Glycosylation1641N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 112 By similarity
Disulfide bond182 ↔ 196 Ref.20
Disulfide bond190 ↔ 210 Ref.20
Disulfide bond212 ↔ 221 Ref.20

Natural variations

Alternative sequence1 – 166166Missing in isoform 10.
VSP_037562
Alternative sequence1 – 3333MSERK…GSQSP → MRWRRAPRRSGRPGPRAQRP GSAARSSPPLPLLPLLLLLG TAALAPGAAAGNEAAPAGAS VCYSSPPSVGSVQELAQRAA VVIEGKVHPQRRQQGALDRK AAAAAGEAGAWGGDREPPAA GPRALGPPAEEPLLAANGTV PSWPTAPVPSAGEPGEEAPY LVKVHQVWAVKAGGLKKDSL LTVRLGTWGHPAFPSCGRLK EDSRYIFFMEPDANSTSRAP AAFRASFPPLETGRNLKKEV SRVLCKRC in isoform 9.
VSP_003425
Alternative sequence1 – 2121Missing in isoform 11.
VSP_037563
Alternative sequence22 – 3312KKPES…GSQSP → MGKGRAGRVGTT in isoform 11.
VSP_037564
Alternative sequence134 – 16835EIITG…NTSSS → A in isoform 9 and isoform 11.
VSP_003426
Alternative sequence1671S → MEIYSPDMSEVAAERSSSPS TQLSADPSLDGLPAAEDMPE PQTEDGRTPGLVGLAVPCCA CLEAERLRGCLNSEKICIVP ILACLVSLCLCIAGLKWVFV DKIFEYDSPTHLDPGGLGQD PIISLDATAASAVWVSSEAY TSPVSRAQSESEVQVTVQGD KAVVSFEPSAAPTPKNRIFA FSFLPSTAPSFPSPTRNPEV RTPKSATQPQTTETNLQTAP KL in isoform 10.
VSP_037565
Alternative sequence213 – 24129QPGFT…ELYQK → PNEFTGDRCQNYVMASFYST STPFLSLPE in isoform 8, isoform 9 and isoform 10.
VSP_003429
Alternative sequence213 – 23422QPGFT…QNQEK → PNEFTGDRCQNYVMASFYKH LGIEFME in isoform 6 and isoform 11.
VSP_003428
Alternative sequence213 – 23321QPGFT…VQNQE → PNEFTGDRCQNYVMASFY in isoform 7 and isoform 12.
VSP_003427
Alternative sequence234 – 24714KAEEL…VLTIT → SAQMSLLVIAAKTT in isoform 4.
VSP_003432
Alternative sequence2341K → KHLGIEFIE in isoform 2.
VSP_003431
Alternative sequence242 – 640399Missing in isoform 8, isoform 9 and isoform 10.
VSP_003430
Alternative sequence248 – 640393Missing in isoform 4.
VSP_003433
Alternative sequence424 – 640217Missing in isoform 12.
VSP_046417
Alternative sequence424 – 46239YVSAM…SMTVS → HNLIAELRRNKAHRSKCMQI QLSATHLRSSSIPHLGFIL in isoform 3.
VSP_003434
Alternative sequence463 – 640178Missing in isoform 3.
VSP_003435
Natural variant381R → Q. Ref.10
Corresponds to variant rs3924999 [ dbSNP | Ensembl ].
VAR_009307
Natural variant2891M → T. Ref.5 Ref.10
Corresponds to variant rs10503929 [ dbSNP | Ensembl ].
VAR_053531
Natural variant4631M → K.
VAR_009308
Isoform 10:
Natural variant461G → R.
Corresponds to variant rs3735774 [ dbSNP | Ensembl ].
Natural variant1271A → P.
Corresponds to variant rs34822181 [ dbSNP | Ensembl ].

Experimental info

Sequence conflict941K → A in AAA19953. Ref.2
Sequence conflict1071S → P in ABQ53539. Ref.10
Sequence conflict2611V → L in ABQ53540. Ref.10
Sequence conflict4141S → F in AAA19953. Ref.2
Sequence conflict5351Q → R in AAA19951. Ref.2

Secondary structure

............... 640
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: C30D3F614AADFF62

FASTA64070,392
        10         20         30         40         50         60 
MSERKEGRGK GKGKKKERGS GKKPESAAGS QSPALPPRLK EMKSQESAAG SKLVLRCETS 

        70         80         90        100        110        120 
SEYSSLRFKW FKNGNELNRK NKPQNIKIQK KPGKSELRIN KASLADSGEY MCKVISKLGN 

       130        140        150        160        170        180 
DSASANITIV ESNEIITGMP ASTEGAYVSS ESPIRISVST EGANTSSSTS TSTTGTSHLV 

       190        200        210        220        230        240 
KCAEKEKTFC VNGGECFMVK DLSNPSRYLC KCQPGFTGAR CTENVPMKVQ NQEKAEELYQ 

       250        260        270        280        290        300 
KRVLTITGIC IALLVVGIMC VVAYCKTKKQ RKKLHDRLRQ SLRSERNNMM NIANGPHHPN 

       310        320        330        340        350        360 
PPPENVQLVN QYVSKNVISS EHIVEREAET SFSTSHYTST AHHSTTVTQT PSHSWSNGHT 

       370        380        390        400        410        420 
ESILSESHSV IVMSSVENSR HSSPTGGPRG RLNGTGGPRE CNSFLRHARE TPDSYRDSPH 

       430        440        450        460        470        480 
SERYVSAMTT PARMSPVDFH TPSSPKSPPS EMSPPVSSMT VSMPSMAVSP FMEEERPLLL 

       490        500        510        520        530        540 
VTPPRLREKK FDHHPQQFSS FHHNPAHDSN SLPASPLRIV EDEEYETTQE YEPAQEPVKK 

       550        560        570        580        590        600 
LANSRRAKRT KPNGHIANRL EVDSNTSSQS SNSESETEDE RVGEDTPFLG IQNPLAASLE 

       610        620        630        640 
ATPAFRLADS RTNPAGRFST QEEIQARLSS VIANQDPIAV 

« Hide

Isoform 2 (Alpha1A) [UniParc].

Checksum: 775329E1F5FED358
Show »

FASTA64871,331
Isoform 3 (Alpha2B) [UniParc].

Checksum: 00F513509DED3269
Show »

FASTA46250,879
Isoform 4 (Alpha3) [UniParc].

Checksum: 8D44247649C60C67
Show »

FASTA24726,590
Isoform 6 (Beta1) (Beta1A) [UniParc].

Checksum: D61555DF50325386
Show »

FASTA64571,157
Isoform 7 (Beta2) [UniParc].

Checksum: D92B25445628869D
Show »

FASTA63770,200
Isoform 8 (Beta3) (GGFHFB1) [UniParc].

Checksum: D2450DB340E6B64D
Show »

FASTA24126,143
Isoform 9 (GGF2) (GGFHPP2) [UniParc].

Checksum: 3535A1E4AB8EEA8E
Show »

FASTA42245,141
Isoform 10 (SMDF) [UniParc].

Checksum: 8D41743217F7EB02
Show »

FASTA29631,686
Isoform 11 (Type IV-beta1a) [UniParc].

Checksum: B4DCA7D49EE8117B
Show »

FASTA59065,460
Isoform 12 [UniParc].

Checksum: BE6F4EBA41F043A9
Show »

FASTA42046,226

References

« Hide 'large scale' references
[1]"Identification of heregulin, a specific activator of p185erbB2."
Holmes W.E., Sliwkowski M.X., Akita R.W., Henzel W.J., Lee J., Park J.W., Yansura D., Abadi N., Raab H., Lewis G.D., Shepard H.M., Kuang W.-J., Wood W.I., Goeddel D.V., Vandlen R.L.
Science 256:1205-1210(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 6; 7 AND 8), PARTIAL PROTEIN SEQUENCE.
[2]"Structural and functional aspects of the multiplicity of Neu differentiation factors."
Wen D., Suggs S.V., Karunagaran D., Liu N., Cupples R.L., Luo Y., Janssen A.M., Ben-Baruch N., Trollinger D.B., Jacobsen V.L., Meng S.-Y., Lu H.S., Hu S., Chang D., Yang W., Yanigahara D., Koski R.A., Yarden Y.
Mol. Cell. Biol. 14:1909-1919(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 6; 7 AND 8).
Tissue: Kidney adenocarcinoma and Pituitary.
[3]"Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system."
Marchionni M.A., Goodearl A.D.J., Chen M.S., Bermingham-McDonogh O., Kirk C., Hendricks M., Danehy F., Misumi D., Sudhalter J., Kobayashi K., Wroblewski D., Lynch C., Baldasarre M., Hiles I., Davis J.B., Hsuan J.J., Totty N.F., Otsu M. expand/collapse author list , McBurney R.N., Waterfield M.D., Stroobant P., Gwynne D.
Nature 362:312-318(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 8 AND 9).
Tissue: Brain.
[4]"Sensory and motor neuron-derived factor. A novel heregulin variant highly expressed in sensory and motor neurons."
Ho W.-H., Armanini M.P., Nuijens A., Phillips H.S., Osheroff P.L.
J. Biol. Chem. 270:14523-14532(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10).
Tissue: Brain stem and Cerebellum.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 10 AND 12), VARIANT THR-289.
Tissue: Hippocampus.
[6]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"Gamma-heregulin: a novel heregulin isoform that is an autocrine growth factor for the human breast cancer cell line, MDA-MB-175."
Schaefer G., Fitzpatrick V.D., Sliwkowski M.X.
Oncogene 15:1385-1394(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF GAMMA-HEREGULIN FUSION PROTEIN.
Tissue: Mammary cancer.
[9]"Neuregulin 1 and susceptibility to Schizophrenia."
Stefansson H., Sigurdsson E., Steinthorsdottir V., Bjornsdottir S., Sigmundsson T., Ghosh S., Brynjolfsson J., Gunnarsdottir S., Ivarsson O., Chou T.T., Hjaltason O., Birgisdottir B., Jonsson H., Gudnadottir V.G., Gudmundsdottir E., Bjornsson A., Ingvarsson B., Ingason A. expand/collapse author list , Sigfusson S., Hardardottir H., Harvey R.P., Brunner D., Mutel V., Gonzalo A., Lemke G., Sainz J., Johannesson G., Andresson T., Gudbjartsson D., Manolescu A., Frigge M.L., Gurney M.E., Kong A., Gulcher J.R., Petursson H., Stefansson K.
Am. J. Hum. Genet. 71:877-892(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 3; 8 AND 9), SUSCEPTIBILITY TO SCHIZOPHRENIA.
[10]"Molecular cloning of a brain-specific, developmentally regulated neuregulin 1 (NRG1) isoform and identification of a functional promoter variant associated with schizophrenia."
Tan W., Wang Y., Gold B., Chen J., Dean M., Harrison P.J., Weinberger D.R., Law A.J.
J. Biol. Chem. 282:24343-24351(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11), ALTERNATIVE SPLICING, VARIANTS GLN-38 AND THR-289, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Tissue: Hippocampus and Prefrontal cortex.
[11]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 10).
Tissue: Brain and Duodenum.
[12]Schoumacher F., Herzer S., Flury N., Kueng W., Mueller H., Eppenberger U.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-211 (ISOFORM 1).
[13]"Characterization of a breast cancer cell differentiation factor that specifically activates the HER4/p180erbB4 receptor."
Culouscou J.-M., Plowman G.D., Carlton G.W., Green J.M., Shoyab M.
J. Biol. Chem. 268:18407-18410(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-28.
[14]"Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells."
Peles E., Bacus S.S., Koski R.A., Lu H.S., Wen D., Ogden S.G., Levy R.B., Yarden Y.
Cell 69:205-216(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE (ISOFORM 1), FUNCTION, GLYCOSYLATION.
[15]"Heregulin induces tyrosine phosphorylation of HER4/p180erbB4."
Plowman G.D., Green J.M., Culouscou J.M., Carlton G.W., Rothwell V.M., Buckley S.
Nature 366:473-475(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ERBB4, FUNCTION.
[16]"Gamma-heregulin is the product of a chromosomal translocation fusing the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell line."
Wang X.-Z., Jolicoeur E.M., Conte N., Chaffanet M., Zhang Y., Mozziconacci M.-J., Feiner H., Birnbaum D., Pebusque M.-J., Ron D.
Oncogene 18:5718-5721(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION.
[17]"Gamma-heregulin: a fusion gene of DOC-4 and neuregulin-1 derived from a chromosome translocation."
Liu X., Baker E., Eyre H.J., Sutherland G.R., Zhou M.
Oncogene 18:7110-7114(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION.
[18]"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.
[19]"Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4."
Nagata K., Kohda D., Hatanaka H., Ichikawa S., Matsuda S., Yamamoto T., Suzuki A., Inagaki F.
EMBO J. 13:3517-3523(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 175-241 (ISOFORM 1).
[20]"High-resolution solution structure of the EGF-like domain of heregulin-alpha."
Jacobsen N.E., Abadi N., Sliwkowski M.X., Reilly D., Skelton N.J., Fairbrother W.J.
Biochemistry 35:3402-3417(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 177-239 (ISOFORM 1), DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Tipping the mind - Issue 129 of June 2011

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M94165 mRNA. Translation: AAA58638.1.
M94166 mRNA. Translation: AAA58639.1.
M94167 mRNA. Translation: AAA58640.1.
M94168 mRNA. Translation: AAA58641.1.
U02325 mRNA. Translation: AAA19950.1.
U02326 mRNA. Translation: AAA19951.1.
U02327 mRNA. Translation: AAA19952.1.
U02328 mRNA. Translation: AAA19953.1.
U02329 mRNA. Translation: AAA19954.1.
U02330 mRNA. Translation: AAA19955.1. Sequence problems.
L12260 mRNA. Translation: AAB59622.1.
L12261 mRNA. Translation: AAB59358.1.
L41827 mRNA. Translation: AAC41764.1.
AK289927 mRNA. Translation: BAF82616.1.
AK298132 mRNA. Translation: BAH12729.1.
AC021909 Genomic DNA. No translation available.
AC022833 Genomic DNA. No translation available.
AC022850 Genomic DNA. No translation available.
AC023948 Genomic DNA. No translation available.
AC068359 Genomic DNA. No translation available.
AC068931 Genomic DNA. No translation available.
AC083977 Genomic DNA. No translation available.
AC103675 Genomic DNA. No translation available.
AC104000 Genomic DNA. No translation available.
AC104029 Genomic DNA. No translation available.
AC113209 Genomic DNA. No translation available.
AF009227 mRNA. Translation: AAC51756.1. Different initiation.
AF491780 Genomic DNA. Translation: AAM71137.1.
AF491780 Genomic DNA. Translation: AAM71139.1.
AF491780 Genomic DNA. Translation: AAM71140.1.
EF372273 mRNA. Translation: ABQ53539.1.
EF372274 mRNA. Translation: ABQ53540.1.
CH471080 Genomic DNA. Translation: EAW63411.1.
BC064587 mRNA. Translation: AAH64587.1.
BC073871 mRNA. Translation: AAH73871.1.
AF026146 mRNA. Translation: AAD01795.1.
BK000383 Genomic DNA. Translation: DAA00044.1.
BK000383 Genomic DNA. Translation: DAA00045.1.
BK000383 Genomic DNA. Translation: DAA00046.1.
BK000383 Genomic DNA. Translation: DAA00047.1.
PIRA43273.
A56943.
B43273.
C43273.
D43273.
I38403.
I38404.
I38408.
S32357.
RefSeqNP_001153467.1. NM_001159995.1.
NP_001153471.1. NM_001159999.1.
NP_001153473.1. NM_001160001.1.
NP_001153477.1. NM_001160005.1.
NP_001153480.1. NM_001160008.1.
NP_039250.2. NM_013956.3.
NP_039251.2. NM_013957.3.
NP_039252.2. NM_013958.3.
NP_039253.1. NM_013959.3.
NP_039254.1. NM_013960.3.
NP_039256.2. NM_013962.2.
NP_039258.1. NM_013964.3.
UniGeneHs.453951.
Hs.668810.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HAENMR-A177-238[»]
1HAFNMR-A177-238[»]
1HRENMR-A175-241[»]
1HRFNMR-A175-241[»]
3U7UX-ray3.03G/H/I/J/K/L175-221[»]
ProteinModelPortalQ02297.
SMRQ02297. Positions 36-131, 175-241.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109332. 5 interactions.
DIPDIP-355N.
IntActQ02297. 5 interactions.
MINTMINT-158528.

PTM databases

PhosphoSiteQ02297.

Polymorphism databases

DMDM9297018.

Proteomic databases

PaxDbQ02297.
PRIDEQ02297.

Protocols and materials databases

DNASU3084.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287842; ENSP00000287842; ENSG00000157168. [Q02297-7]
ENST00000341377; ENSP00000340497; ENSG00000157168. [Q02297-4]
ENST00000356819; ENSP00000349275; ENSG00000157168. [Q02297-6]
ENST00000405005; ENSP00000384620; ENSG00000157168. [Q02297-1]
ENST00000519301; ENSP00000429582; ENSG00000157168. [Q02297-11]
ENST00000520407; ENSP00000434640; ENSG00000157168. [Q02297-9]
ENST00000520502; ENSP00000433289; ENSG00000157168. [Q02297-10]
ENST00000521670; ENSP00000428828; ENSG00000157168. [Q02297-3]
ENST00000523079; ENSP00000430120; ENSG00000157168. [Q02297-12]
GeneID3084.
KEGGhsa:3084.
UCSCuc003xip.3. human. [Q02297-9]
uc003xis.3. human. [Q02297-8]
uc003xit.2. human. [Q02297-3]
uc003xiu.2. human. [Q02297-6]
uc003xiv.2. human. [Q02297-1]
uc003xiw.2. human. [Q02297-7]
uc003xix.3. human. [Q02297-4]
uc003xiy.3. human. [Q02297-10]
uc003xja.2. human. [Q02297-2]
uc010lvp.2. human. [Q02297-11]

Organism-specific databases

CTD3084.
GeneCardsGC08P031554.
HGNCHGNC:7997. NRG1.
HPAHPA010964.
MIM142445. gene.
neXtProtNX_Q02297.
PharmGKBPA31776.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47801.
HOVERGENHBG006531.
KOK05455.
OrthoDBEOG7F7W86.
TreeFamTF332469.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkQ02297.

Gene expression databases

ArrayExpressQ02297.
BgeeQ02297.
CleanExHS_NRG1.
GenevestigatorQ02297.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR018250. Neuregulin.
IPR002154. Neuregulin_1_C.
[Graphical view]
PfamPF12661. hEGF. 1 hit.
PF07679. I-set. 1 hit.
PF02158. Neuregulin. 1 hit.
[Graphical view]
PRINTSPR01089. NEUREGULIN.
SMARTSM00181. EGF. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNRG1. human.
EvolutionaryTraceQ02297.
GeneWikiNeuregulin_1.
GenomeRNAi3084.
NextBio12227.
PMAP-CutDBQ02297.
PROQ02297.
SOURCESearch...

Entry information

Entry nameNRG1_HUMAN
AccessionPrimary (citable) accession number: Q02297
Secondary accession number(s): A5YAK4 expand/collapse secondary AC list , A5YAK5, A8K1L2, B7Z4Z3, E9PHH4, O14667, P98202, Q02298, Q02299, Q07110, Q07111, Q12779, Q12780, Q12781, Q12782, Q12783, Q12784, Q15491, Q7RTV9, Q7RTW0, Q7RTW1, Q7RTW2, Q8NFN1, Q8NFN2, Q8NFN3, Q9UPE3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM