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Protein

Pro-neuregulin-2, membrane-bound isoform

Gene

Nrg2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. May also promote the heterodimerization with the EGF receptor.

GO - Molecular functioni

  • epidermal growth factor-activated receptor activity Source: RGD
  • epidermal growth factor receptor binding Source: RGD
  • ErbB-3 class receptor binding Source: RGD

GO - Biological processi

  • epidermal growth factor receptor signaling pathway Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Names & Taxonomyi

Protein namesi
Recommended name:
Pro-neuregulin-2, membrane-bound isoform
Short name:
Pro-NRG2
Cleaved into the following chain:
Neuregulin-2
Short name:
NRG-2
Alternative name(s):
Neural- and thymus-derived activator for ERBB kinases
Short name:
NTAK
Gene namesi
Name:Nrg2
Synonyms:Ntak
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1303302. Nrg2.

Subcellular locationi

Pro-neuregulin-2, membrane-bound isoform :
Neuregulin-2 :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini128 – 429302ExtracellularSequence analysisAdd
BLAST
Transmembranei430 – 45021Helical; Note=Internal signal sequenceSequence analysisAdd
BLAST
Topological domaini451 – 868418CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 1271271 PublicationPRO_0000019478Add
BLAST
Chaini128 – 868741Pro-neuregulin-2, membrane-bound isoformPRO_0000019479Add
BLAST
Chaini128 – 428301Neuregulin-2PRO_0000019480Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi33 – 331N-linked (GlcNAc...)Sequence analysis
Glycosylationi34 – 341N-linked (GlcNAc...)Sequence analysis
Glycosylationi163 – 1631N-linked (GlcNAc...)Sequence analysis
Disulfide bondi273 ↔ 327By similarity
Glycosylationi294 – 2941N-linked (GlcNAc...)Sequence analysis
Disulfide bondi361 ↔ 375By similarity
Glycosylationi362 – 3621N-linked (GlcNAc...)Sequence analysis
Disulfide bondi369 ↔ 386By similarity
Disulfide bondi388 ↔ 397By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO35569.

Expressioni

Tissue specificityi

Expressed in most parts of the brain, especially the olfactory bulb and cerebellum where it localizes in granule and Purkinje cells. In the hippocampus, found in the granule cells of the dentate gyrus. In the basal forebrain, found in the cholinergic cells. In the hindbrain, weakly detectable in the motor trigeminal nucleus. Not detected in the hypothalamus. Also found in the liver and in the thymus. Not detected in heart, adrenal gland, or testis.

Developmental stagei

In the embryo, expressed in the brain of E11.5 embryos where it is found in the telencephalon, but not in the hindbrain. Not found in the heart. In the adult, found in brain and thymus.

Interactioni

Subunit structurei

Interacts with ERBB3 and ERBB4.

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: RGD
  • ErbB-3 class receptor binding Source: RGD

Protein-protein interaction databases

MINTiMINT-4996176.
STRINGi10116.ENSRNOP00000025901.

Structurei

3D structure databases

ProteinModelPortaliO35569.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini253 – 34896Ig-like C2-typeAdd
BLAST
Domaini357 – 39842EGF-likePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi22 – 3211Poly-SerAdd
BLAST
Compositional biasi35 – 4511Poly-SerAdd
BLAST
Compositional biasi56 – 594Poly-Thr
Compositional biasi103 – 1064Poly-Ala
Compositional biasi346 – 35611Ser/Thr-richAdd
BLAST
Compositional biasi739 – 7457Poly-Pro

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.By similarity

Sequence similaritiesi

Belongs to the neuregulin family.Curated
Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Immunoglobulin domain, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGZW. Eukaryota.
ENOG410Y95Z. LUCA.
HOGENOMiHOG000273863.
HOVERGENiHBG006531.
InParanoidiO35569.
KOiK05456.
PhylomeDBiO35569.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR002154. Neuregulin_C.
[Graphical view]
PfamiPF07679. I-set. 1 hit.
PF02158. Neuregulin. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. The alpha-type and beta-type differ in the EGF-like domain.

Isoform 1 (identifier: O35569-1) [UniParc]FASTAAdd to basket

Also known as: NTAK-alpha1

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.

« Hide

        10         20         30         40         50
MRQVCCSALP PPLEKARCSS YSYSDSSSSS SSNNSSSSTS SRSSSRSSSR
60 70 80 90 100
SSRGSTTTTS SSENSGSNSG SIFRPAAPPE PRPQPQPQPR SPAARRAAAR
110 120 130 140 150
SRAAAAGGMR RDPAPGSSML LFGVSLACYS PSLKSVQDQA YKAPVVVEGK
160 170 180 190 200
VQGLAPAGGS SSNSTREPPA SGRVALVKVL DKWPLRSGGL QREQVISVGS
210 220 230 240 250
CAPLERNQRY IFFLEPTEQP LVFKTAFAPV DPNGKNIKKE VGKILCTDCA
260 270 280 290 300
TRPKLKKMKS QTGEVGEKQS LKCEAAAGNP QPSYRWFKDG KELNRSRDIR
310 320 330 340 350
IKYGNGRKNS RLQFNKVKVE DAGEYVCEAE NILGKDTVRG RLHVNSVSTT
360 370 380 390 400
LSSWSGHARK CNETAKSYCV NGGVCYYIEG INQLSCKCPN GFFGQRCLEK
410 420 430 440 450
LPLRLYMPDP KQKHLGFELK EAEELYQKRV LTITGICVAL LVVGIVCVVA
460 470 480 490 500
YCKTKKQRRQ MHHHLRQNMC PAHQNRSLAN GPSHPRLDPE EIQMADYISK
510 520 530 540 550
NVPATDHVIR REAETTFSGS HSCSPSHHCS TATPTSSHRH ESHTWSLERS
560 570 580 590 600
ESLTSDSQSG IMLSSVGTSK CNSPACVEAR ARRAAAYSQE ERRRAAMPPY
610 620 630 640 650
HDSIDSLRDS PHSERYVSAL TTPARLSPVD FHYSLATQVP TFEITSPNSA
660 670 680 690 700
HAVSLPPAAP ISYRLAEQQP LLRHPAPPGP GPGPGADMQR SYDSYYYPAA
710 720 730 740 750
GPGPRRGACA LGGSLGSLPA SPFRIPEDDE YETTQECAPP PPPRPRTRGA
760 770 780 790 800
SRRTSAGPRR WRRSRLNGLA AQRARAARDS LSLSSGSGCG SASASDDDAD
810 820 830 840 850
DADGALAAES TPFLGLRAAH DALRSDSPPL CPAADSRTYY SLDSHSTRAS
860
SRHSRGPPTR AKQDSGPL
Length:868
Mass (Da):93,777
Last modified:January 1, 1998 - v1
Checksum:i3C7D4D94DBE64DE2
GO
Isoform 2 (identifier: O35569-2) [UniParc]FASTAAdd to basket

Also known as: NTAK-alpha2A

The sequence of this isoform differs from the canonical sequence as follows:
     414-421: Missing.

Show »
Length:860
Mass (Da):92,823
Checksum:iEA4BDB193DDAFFC7
GO
Isoform 3 (identifier: O35569-3) [UniParc]FASTAAdd to basket

Also known as: NTAK-alpha2B, NTAK-alpha2-1P

The sequence of this isoform differs from the canonical sequence as follows:
     220-222: PLV → FFF
     414-421: Missing.

Show »
Length:860
Mass (Da):92,955
Checksum:iE14192395B98AE9E
GO
Isoform 4 (identifier: O35569-4) [UniParc]FASTAAdd to basket

Also known as: NTAK-beta

The sequence of this isoform differs from the canonical sequence as follows:
     390-421: NGFFGQRCLEKLPLRLYMPDPKQKHLGFELKE → VGYTGDRCQQFAMVNFSK

Show »
Length:854
Mass (Da):91,995
Checksum:iF78A98550A869D4A
GO
Isoform 5 (identifier: O35569-5) [UniParc]FASTAAdd to basket

Also known as: NTAK-gamma

The sequence of this isoform differs from the canonical sequence as follows:
     388-388: C → G
     389-868: Missing.

Show »
Length:388
Mass (Da):41,620
Checksum:i848108D986E87F7F
GO
Isoform 6 (identifier: O35569-6) [UniParc]FASTAAdd to basket

Also known as: NRG2-alpha

The sequence of this isoform differs from the canonical sequence as follows:
     414-439: HLGFELKEAEELYQKRVLTITGICVA → SVLWDTPGTGVSSSQWSTSPSTLDLN
     440-868: Missing.

Show »
Length:439
Mass (Da):47,329
Checksum:i82D98EFB30FE37FD
GO
Isoform 7 (identifier: O35569-7) [UniParc]FASTAAdd to basket

Also known as: NRG2-beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.
     390-412: NGFFGQRCLEKLPLRLYMPDPKQ → VGYTGDRCQQFAMVNFS

Show »
Length:754
Mass (Da):81,951
Checksum:iBE1E4E3548FE65E2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti117 – 1171S → F (PubMed:9168114).Curated
Sequence conflicti724 – 7241R → H (PubMed:9168114).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 108108Missing in isoform 7. 1 PublicationVSP_003465Add
BLAST
Alternative sequencei220 – 2223PLV → FFF in isoform 3. CuratedVSP_003466
Alternative sequencei388 – 3881C → G in isoform 5. CuratedVSP_003467
Alternative sequencei389 – 868480Missing in isoform 5. CuratedVSP_003468Add
BLAST
Alternative sequencei390 – 42132NGFFG…FELKE → VGYTGDRCQQFAMVNFSK in isoform 4. CuratedVSP_003470Add
BLAST
Alternative sequencei390 – 41223NGFFG…PDPKQ → VGYTGDRCQQFAMVNFS in isoform 7. 1 PublicationVSP_003469Add
BLAST
Alternative sequencei414 – 43926HLGFE…GICVA → SVLWDTPGTGVSSSQWSTSP STLDLN in isoform 6. 1 PublicationVSP_003472Add
BLAST
Alternative sequencei414 – 4218Missing in isoform 2 and isoform 3. CuratedVSP_003471
Alternative sequencei440 – 868429Missing in isoform 6. 1 PublicationVSP_003473Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89995 mRNA. Translation: BAA23344.1.
D89996 mRNA. Translation: BAA23345.1.
D89997 mRNA. Translation: BAA23346.1.
D89998 mRNA. Translation: BAA23347.1.
AB001576 mRNA. Translation: BAA23348.1.
PIRiJC5701.
JC5702.
RefSeqiNP_001129623.1. NM_001136151.1. [O35569-2]
UniGeneiRn.22434.

Genome annotation databases

GeneIDi432361.
KEGGirno:432361.
UCSCiRGD:1303302. rat. [O35569-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89995 mRNA. Translation: BAA23344.1.
D89996 mRNA. Translation: BAA23345.1.
D89997 mRNA. Translation: BAA23346.1.
D89998 mRNA. Translation: BAA23347.1.
AB001576 mRNA. Translation: BAA23348.1.
PIRiJC5701.
JC5702.
RefSeqiNP_001129623.1. NM_001136151.1. [O35569-2]
UniGeneiRn.22434.

3D structure databases

ProteinModelPortaliO35569.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4996176.
STRINGi10116.ENSRNOP00000025901.

Proteomic databases

PaxDbiO35569.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi432361.
KEGGirno:432361.
UCSCiRGD:1303302. rat. [O35569-1]

Organism-specific databases

CTDi9542.
RGDi1303302. Nrg2.

Phylogenomic databases

eggNOGiENOG410IGZW. Eukaryota.
ENOG410Y95Z. LUCA.
HOGENOMiHOG000273863.
HOVERGENiHBG006531.
InParanoidiO35569.
KOiK05456.
PhylomeDBiO35569.

Miscellaneous databases

PROiO35569.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR002154. Neuregulin_C.
[Graphical view]
PfamiPF07679. I-set. 1 hit.
PF02158. Neuregulin. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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], PROTEIN SEQUENCE OF 128-162, ALTERNATIVE SPLICING.
  2. "Ligands for ErbB-family receptors encoded by a neuregulin-like gene."
    Chang H., Riese D.J. II, Gilbert W., Stern D.F., McMahan U.J.
    Nature 387:509-512(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 109-868 (ISOFORMS 6 AND 7).
    Tissue: Cerebellum.

Entry informationi

Entry nameiNRG2_RAT
AccessioniPrimary (citable) accession number: O35569
Secondary accession number(s): O35073
, O35570, O35571, O35572
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 1, 1998
Last modified: June 8, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.