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O14511 (NRG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pro-neuregulin-2, membrane-bound isoform

Short name=Pro-NRG2

Cleaved into the following chain:

  1. Neuregulin-2
    Short name=NRG-2
    Alternative name(s):
    Divergent of neuregulin-1
    Short name=DON-1
    Neural- and thymus-derived activator for ERBB kinases
    Short name=NTAK
Gene names
Name:NRG2
Synonyms:NTAK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length850 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. May also promote the heterodimerization with the EGF receptor.

Subunit structure

Interacts with ERBB3 and ERBB4. Ref.4

Subcellular location

Pro-neuregulin-2, membrane-bound isoform: Cell membrane; Single-pass type I membrane protein By similarity. Note: Does not seem to be active By similarity.

Neuregulin-2: Secreted By similarity.

Tissue specificity

Restricted to the cerebellum in the adult.

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 By similarity.

Post-translational modification

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.

Sequence similarities

Belongs to the neuregulin family.

Contains 1 EGF-like domain.

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

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14511-1)

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: O14511-2)

The sequence of this isoform differs from the canonical sequence as follows:
     374-396: NGFFGQRCLEKLPLRLYMPDPKQ → VGYTGDRCQQFAMVNFS
Note: No experimental confirmation available.
Isoform 3 (identifier: O14511-3)

The sequence of this isoform differs from the canonical sequence as follows:
     397-397: K → KHLGFELKE
Note: No experimental confirmation available.
Isoform 4 (identifier: O14511-4)

The sequence of this isoform differs from the canonical sequence as follows:
     374-397: NGFFGQRCLEKLPLRLYMPDPKQK → VGYTGDRCQQFAMVNFSKHLGFELKE
Note: No experimental confirmation available.
Isoform 5 (identifier: O14511-5)

The sequence of this isoform differs from the canonical sequence as follows:
     397-426: KAEELYQKRVLTITGICVALLVVGIVCVVA → SVLWDTPGTGVSSSQWSTSPKPRSCTRRGS
     427-850: Missing.
Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 6 (identifier: O14511-6)

The sequence of this isoform differs from the canonical sequence as follows:
     397-422: KAEELYQKRVLTITGICVALLVVGIV → SVLWDTPGTGVSSSQWSTSPSTLDLN
     423-850: Missing.
Note: No experimental confirmation available.
Isoform DON-1B (identifier: O14511-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-241: Missing.
     397-397: K → KHLGFELKE
Isoform DON-1R (identifier: O14511-8)

The sequence of this isoform differs from the canonical sequence as follows:
     1-233: MRQVCCSALP...EVGKILCTDC → MSESRRRGRGRGKKHPEGRKREREPDPGEK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 111111 By similarity
PRO_0000019472
Chain112 – 850739Pro-neuregulin-2, membrane-bound isoform
PRO_0000019473
Chain112 – 404293Neuregulin-2
PRO_0000019474

Regions

Topological domain112 – 405294Extracellular Potential
Transmembrane406 – 42621Helical; Note=Internal signal sequence; Potential
Topological domain427 – 850424Cytoplasmic Potential
Domain237 – 33296Ig-like C2-type
Domain341 – 38242EGF-like
Compositional bias10 – 134Poly-Pro
Compositional bias20 – 3011Poly-Ser
Compositional bias33 – 4715Poly-Ser
Compositional bias87 – 904Poly-Ala
Compositional bias330 – 34011Ser/Thr-rich
Compositional bias721 – 7277Poly-Pro

Amino acid modifications

Glycosylation521N-linked (GlcNAc...) Potential
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation1471N-linked (GlcNAc...) Potential
Glycosylation2781N-linked (GlcNAc...) Potential
Glycosylation3461N-linked (GlcNAc...) Potential
Disulfide bond257 ↔ 311 By similarity
Disulfide bond345 ↔ 359 By similarity
Disulfide bond353 ↔ 370 By similarity
Disulfide bond372 ↔ 381 By similarity

Natural variations

Alternative sequence1 – 241241Missing in isoform DON-1B.
VSP_003452
Alternative sequence1 – 233233MRQVC…LCTDC → MSESRRRGRGRGKKHPEGRK REREPDPGEK in isoform DON-1R.
VSP_003451
Alternative sequence374 – 39724NGFFG…DPKQK → VGYTGDRCQQFAMVNFSKHL GFELKE in isoform 4.
VSP_003454
Alternative sequence374 – 39623NGFFG…PDPKQ → VGYTGDRCQQFAMVNFS in isoform 2.
VSP_003453
Alternative sequence397 – 42630KAEEL…VCVVA → SVLWDTPGTGVSSSQWSTSP KPRSCTRRGS in isoform 5.
VSP_003458
Alternative sequence397 – 42226KAEEL…VVGIV → SVLWDTPGTGVSSSQWSTSP STLDLN in isoform 6.
VSP_003456
Alternative sequence3971K → KHLGFELKE in isoform 3 and isoform DON-1B.
VSP_003455
Alternative sequence423 – 850428Missing in isoform 6.
VSP_003457
Alternative sequence427 – 850424Missing in isoform 5.
VSP_003459

Sequences

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

Last modified January 1, 1998. Version 1.
Checksum: 7124C089435FD2F4

FASTA85091,679
        10         20         30         40         50         60 
MRQVCCSALP PPPLEKGRCS SYSDSSSSSS ERSSSSSSSS SESGSSSRSS SNNSSISRPA 

        70         80         90        100        110        120 
APPEPRPQQQ PQPRSPAARR AAARSRAAAA GGMRRDPAPG FSMLLFGVSL ACYSPSLKSV 

       130        140        150        160        170        180 
QDQAYKAPVV VEGKVQGLVP AGGSSSNSTR EPPASGRVAL VKVLDKWPLR SGGLQREQVI 

       190        200        210        220        230        240 
SVGSCVPLER NQRYIFFLEP TEQPLVFKTA FAPLDTNGKN LKKEVGKILC TDCATRPKLK 

       250        260        270        280        290        300 
KMKSQTGQVG EKQSLKCEAA AGNPQPSYRW FKDGKELNRS RDIRIKYGNG RKNSRLQFNK 

       310        320        330        340        350        360 
VKVEDAGEYV CEAENILGKD TVRGRLYVNS VSTTLSSWSG HARKCNETAK SYCVNGGVCY 

       370        380        390        400        410        420 
YIEGINQLSC KCPNGFFGQR CLEKLPLRLY MPDPKQKAEE LYQKRVLTIT GICVALLVVG 

       430        440        450        460        470        480 
IVCVVAYCKT KKQRKQMHNH LRQNMCPAHQ NRSLANGPSH PRLDPEEIQM ADYISKNVPA 

       490        500        510        520        530        540 
TDHVIRRETE TTFSGSHSCS PSHHCSTATP TSSHRHESHT WSLERSESLT SDSQSGIMLS 

       550        560        570        580        590        600 
SVGTSKCNSP ACVEARARRA AAYNLEERRR ATAPPYHDSV DSLRDSPHSE RYVSALTTPA 

       610        620        630        640        650        660 
RLSPVDFHYS LATQVPTFEI TSPNSAHAVS LPPAAPISYR LAEQQPLLRH PAPPGPGPGP 

       670        680        690        700        710        720 
GPGPGPGADM QRSYDSYYYP AAGPGPRRGT CALGGSLGSL PASPFRIPED DEYETTQECA 

       730        740        750        760        770        780 
PPPPPRPRAR GASRRTSAGP RRWRRSRLNG LAAQRARAAR DSLSLSSGSG GGSASASDDD 

       790        800        810        820        830        840 
ADDADGALAA ESTPFLGLRG AHDALRSDSP PLCPAADSRT YYSLDSHSTR ASSRHSRGPP 

       850 
PRAKQDSAPL 

« Hide

Isoform 2 [UniParc].

Checksum: A68F2D2C96C3C1C1
Show »

FASTA84490,851
Isoform 3 [UniParc].

Checksum: 171976A9397EA0B1
Show »

FASTA85892,633
Isoform 4 [UniParc].

Checksum: FDE8AEB0E1C6F94B
Show »

FASTA85291,805
Isoform 5 [UniParc].

Checksum: ADC950AED919D5F4
Show »

FASTA42646,183
Isoform 6 [UniParc].

Checksum: 5CF05AF7A682310D
Show »

FASTA42245,698
Isoform DON-1B [UniParc].

Checksum: 89A81CE27CE00B5C
Show »

FASTA61767,126
Isoform DON-1R [UniParc].

Checksum: D1D5FDAF07CB3393
Show »

FASTA64770,637

References

[1]"A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4."
Higashiyama S., Horikawa M., Yamada K., Ichino N., Nakano N., Nakagawa T., Miyagawa J., Matsushita N., Nagatsu T., Taniguchi N., Ishiguro H.
J. Biochem. 122:675-680(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Neuroblastoma.
[2]"Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus."
Busfield S.J., Michnick D.A., Chickering T.W., Revett T.L., Ma J., Woolf E.A., Comrack C.A., Dussault B.J., Woolf J., Goodearl A.D.J., Gearing D.P.
Mol. Cell. Biol. 17:4007-4014(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS DON-1B AND DON-1R).
Tissue: Fetal brain.
[3]"The human neuregulin 2 (NRG2) gene: cloning, mapping and evaluation as a candidate for the autosomal recessive form of Charcot-Marie-Tooth disease linked to 5q."
Ring H.Z., Chang H., Guilbot A., Brice A., LeGuern E., Francke U.
Hum. Genet. 104:326-332(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3; 4; 5 AND 6).
Tissue: Fetal brain and Lung.
[4]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB005060 mRNA. Translation: BAA23417.1.
AF119162 expand/collapse EMBL AC list , AF119151, AF119152, AF119153, AF119154, AF119155, AF119158, AF119159, AF119160, AF119161 Genomic DNA. Translation: AAF28848.1.
AF119162 expand/collapse EMBL AC list , AF119151, AF119152, AF119153, AF119154, AF119156, AF119158, AF119159, AF119160, AF119161 Genomic DNA. Translation: AAF28849.1.
AF119162 expand/collapse EMBL AC list , AF119151, AF119152, AF119153, AF119154, AF119155, AF119157, AF119158, AF119159, AF119160, AF119161 Genomic DNA. Translation: AAF28850.1.
AF119162 expand/collapse EMBL AC list , AF119151, AF119152, AF119153, AF119154, AF119156, AF119157, AF119158, AF119159, AF119160, AF119161 Genomic DNA. Translation: AAF28851.1.
AF119158 expand/collapse EMBL AC list , AF119151, AF119152, AF119153, AF119154, AF119155, AF119156 Genomic DNA. Translation: AAF28852.1.
AF119157 expand/collapse EMBL AC list , AF119151, AF119152, AF119153, AF119154, AF119155, AF119156 Genomic DNA. Translation: AAF28853.1.
CCDSCCDS4217.1. [O14511-1]
PIRJC5700.
RefSeqNP_001171864.1. NM_001184935.1.
NP_004874.1. NM_004883.2. [O14511-1]
NP_053584.1. NM_013981.3. [O14511-2]
NP_053585.1. NM_013982.2. [O14511-3]
NP_053586.1. NM_013983.2. [O14511-4]
XP_006714871.1. XM_006714808.1. [O14511-8]
XP_006714873.1. XM_006714810.1. [O14511-6]
UniGeneHs.408515.

3D structure databases

ProteinModelPortalO14511.
SMRO14511. Positions 244-381.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114917. 2 interactions.
STRING9606.ENSP00000289422.

PTM databases

PhosphoSiteO14511.

Proteomic databases

PaxDbO14511.
PRIDEO14511.

Protocols and materials databases

DNASU9542.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000289409; ENSP00000289409; ENSG00000158458. [O14511-2]
ENST00000289422; ENSP00000289422; ENSG00000158458. [O14511-3]
ENST00000340391; ENSP00000342660; ENSG00000158458. [O14511-8]
ENST00000358522; ENSP00000351323; ENSG00000158458. [O14511-4]
ENST00000361474; ENSP00000354910; ENSG00000158458. [O14511-1]
ENST00000378238; ENSP00000367483; ENSG00000158458. [O14511-5]
ENST00000394770; ENSP00000378251; ENSG00000158458. [O14511-5]
GeneID9542.
KEGGhsa:9542.
UCSCuc003lev.2. human. [O14511-3]
uc003lew.2. human. [O14511-4]
uc003lex.2. human. [O14511-1]
uc003ley.2. human. [O14511-2]

Organism-specific databases

CTD9542.
GeneCardsGC05M139207.
HGNCHGNC:7998. NRG2.
HPAHPA038935.
HPA047973.
MIM603818. gene.
neXtProtNX_O14511.
PharmGKBPA31777.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47801.
HOGENOMHOG000273863.
HOVERGENHBG006531.
KOK05456.
OMAKAGGMRL.
OrthoDBEOG7F7W86.
PhylomeDBO14511.
TreeFamTF332469.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkO14511.

Gene expression databases

ArrayExpressO14511.
BgeeO14511.
CleanExHS_NRG2.
GenevestigatorO14511.

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.
IPR002154. Neuregulin_1_C.
[Graphical view]
PfamPF07679. I-set. 1 hit.
PF02158. Neuregulin. 1 hit.
[Graphical view]
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

GeneWikiNRG2.
GenomeRNAi9542.
NextBio35779.
PROO14511.
SOURCESearch...

Entry information

Entry nameNRG2_HUMAN
AccessionPrimary (citable) accession number: O14511
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 129 of the entry and version 1 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

MIM cross-references

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

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM