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Q05199

- NRG1_CHICK

UniProt

Q05199 - NRG1_CHICK

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Protein

Pro-neuregulin-1, membrane-bound isoform

Gene

NRG1

Organism
Gallus gallus (Chicken)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli

Functioni

Direct ligand for the ERBB tyrosine kinase receptors. The multiple isoforms perform diverse functions: cysteine-rich domain containing isoforms (isoform 2-isoform 4) probably regulate the expression of nicotinic acetylcholine receptors at developing interneuronal synapses. Isoform Ig-NRG is required for the initial induction and/or maintenance of the mature levels of acetylcholine receptors at neuromuscular synapses.

GO - Biological processi

  1. embryo development Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiREACT_189763. Signaling by ERBB2.
REACT_194392. GRB2 events in ERBB2 signaling.
REACT_194393. SHC1 events in ERBB4 signaling.
REACT_194394. Signaling by ERBB4.
REACT_194410. SHC1 events in ERBB2 signaling.
REACT_196847. PI3K events in ERBB4 signaling.
REACT_196849. PI3K events in ERBB2 signaling.
REACT_197054. Nuclear signaling by ERBB4.
REACT_198076. Constitutive PI3K/AKT Signaling in Cancer.
REACT_244793. PIP3 activates AKT signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Pro-neuregulin-1, membrane-bound isoform
Short name:
Pro-NRG1
Cleaved into the following chain:
Alternative name(s):
Acetylcholine receptor-inducing activity
Short name:
ARIA
Gene namesi
Name:NRG1
Synonyms:ARIA
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
ProteomesiUP000000539: Chromosome Z

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 206206ExtracellularSequence AnalysisAdd
BLAST
Transmembranei207 – 22923Helical; Note=Internal signal sequenceSequence AnalysisAdd
BLAST
Topological domaini230 – 602373CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 602602Pro-neuregulin-1, membrane-bound isoformPRO_0000019468Add
BLAST
Chaini1 – 205205Neuregulin-1PRO_0000019469Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi21 – 211N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi49 ↔ 105By similarity
Glycosylationi113 – 1131N-linked (GlcNAc...)Sequence Analysis
Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi141 ↔ 155By similarity
Disulfide bondi149 ↔ 169By similarity
Disulfide bondi171 ↔ 180By 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.
Extensive glycosylation precedes the proteolytic cleavage.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ05199.
PRIDEiQ05199.

Expressioni

Developmental stagei

Isoform 2-isoform 4 are detected at embryonic day 4 (ED4) in both visceral and somatic motor neurons of spinal cord and is highest at ED6. Isoform 1 is not expressed until ED 6 in spinal cord. At ED 11 both isoforms display comparable levels.

Gene expression databases

ExpressionAtlasiQ05199. baseline and differential.

Structurei

3D structure databases

ProteinModelPortaliQ05199.
SMRiQ05199. Positions 136-203.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 12395Ig-like C2-typeAdd
BLAST
Domaini137 – 18145EGF-likePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi125 – 13612Ser/Thr-richAdd
BLAST

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
Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiNOG47801.
GeneTreeiENSGT00710000106660.
HOGENOMiHOG000273863.
HOVERGENiHBG006531.
InParanoidiQ05199.
KOiK05455.
PhylomeDBiQ05199.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR000742. 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]
PfamiPF07679. I-set. 1 hit.
PF02158. Neuregulin. 1 hit.
[Graphical view]
PRINTSiPR01089. NEUREGULIN.
SMARTiSM00181. EGF. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
PS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q05199-1) [UniParc]FASTAAdd to Basket

Also known as: ARIA, Ig-NRG

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
MWATSEGPLQ YSLAPTQTDV NSSYNTVPPK LKEMKNQEVA VGQKLVLRCE
60 70 80 90 100
TTSEYPALRF KWLKNGKEIT KKNRPENVKI PKKQKKYSEL HIYRATLADA
110 120 130 140 150
GEYACRVSSK LGNDSTKASV IITDTNATST STTGTSHLTK CDIKQKAFCV
160 170 180 190 200
NGGECYMVKD LPNPPRYLCR CPNEFTGDRC QNYVMASFYK HLGIEFMEAE
210 220 230 240 250
ELYQKRVLTI TGICIALLVV GIMCVVAYCK TKKQRKKLHD RLRQSLRSER
260 270 280 290 300
NNVMNMANGP HHPNPPPDNV QLVNQYVSKN IISSERVVER ETETSFSTSH
310 320 330 340 350
YTSTTHHSMT VTQTPSHSWS NGHTESILSE SHSVLVSSSV ENSRHTSPTG
360 370 380 390 400
PRGRLNGIGG PREGNSFLRH ARETPDSYRD SPHSERYVSA MTTPARMSPV
410 420 430 440 450
DFHTPTSPKS PPSEMSPPVS SLTISIPSVA VSPFMDEERP LLLVTPPRLR
460 470 480 490 500
EKYDNHLQQF NSFHNNPTHE SNSLPPSPLR IVEDEEYETT QEYEPAQEPP
510 520 530 540 550
KKLTNSRRVK RTKPNGHISS RVEVDSDTSS QSTSSESETE DERIGEDTPF
560 570 580 590 600
LSIQNPMATS LEPAAAYRLA ENRTNPANRF STPEELQARL SSVIANQDPI

AV

Note: Contains an Ig-like domain.

Length:602
Mass (Da):67,454
Last modified:November 1, 1996 - v1
Checksum:i4183C0E56CE5D346
GO
Isoform 2 (identifier: Q05199-2) [UniParc]FASTAAdd to Basket

Also known as: CRD-NRG-BETA1A

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: MWATSEGPLQ...ASVIITDTNA → MSEVGTETFP...TNLQTAPKLS

Note: The EGF-like domain is replaced by a cysteine-rich domain (CRD).

Show »
Length:685
Mass (Da):75,415
Checksum:iB2634881D40B3398
GO
Isoform 3 (identifier: Q05199-3) [UniParc]FASTAAdd to Basket

Also known as: CRD-NRG-BETA2A

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: MWATSEGPLQ...ASVIITDTNA → MSEVGTETFP...TNLQTAPKLS
     191-198: Missing.

Note: The EGF-like domain is replaced by a cysteine-rich domain (CRD).

Show »
Length:677
Mass (Da):74,457
Checksum:iD6C0F3C45B64E0EC
GO
Isoform 4 (identifier: Q05199-4) [UniParc]FASTAAdd to Basket

Also known as: CRD-NRG-BETA2B

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: MWATSEGPLQ...ASVIITDTNA → MSEVGTETFP...TNLQTAPKLS
     191-198: Missing.
     388-405: VSAMTTPARMSPVDFHTP → HTPPTSLLLAGKVSLRVS
     406-602: Missing.

Note: The EGF-like domain is replaced by a cysteine-rich domain (CRD).

Show »
Length:480
Mass (Da):52,440
Checksum:i9B95A898A4669A93
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 127127MWATS…TDTNA → MSEVGTETFPSPSAQLSPDA SLGGLPAEENMPGPHREDSR VPGVAGLASTCCVCLEAERL KGCLNSEKICIAPILACLLS LCLCIAGLKWVFVDKIFEYD SPTHLDPGRIGQDPRSTVDP TALSAWVPSEVYASPFPIPS LESKAEVTVQTDSSLVPSRP FLQPSLYNRILDVGLWSSAT PSLSPSSLEPTTASQAQATE TNLQTAPKLS in isoform 2, isoform 3 and isoform 4. 1 PublicationVSP_003445Add
BLAST
Alternative sequencei191 – 1988Missing in isoform 3 and isoform 4. 1 PublicationVSP_003446
Alternative sequencei388 – 40518VSAMT…DFHTP → HTPPTSLLLAGKVSLRVS in isoform 4. 1 PublicationVSP_003447Add
BLAST
Alternative sequencei406 – 602197Missing in isoform 4. 1 PublicationVSP_003448Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11264 mRNA. Translation: AAA49037.1.
AF045654 mRNA. Translation: AAC05670.1.
AF045655 mRNA. Translation: AAC05671.1.
AF045656 mRNA. Translation: AAC05672.1.
PIRiA45769.
RefSeqiNP_989448.1. NM_204117.1. [Q05199-2]
UniGeneiGga.135.

Genome annotation databases

EnsembliENSGALT00000037781; ENSGALP00000036986; ENSGALG00000015422. [Q05199-1]
GeneIDi373906.
KEGGigga:373906.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11264 mRNA. Translation: AAA49037.1 .
AF045654 mRNA. Translation: AAC05670.1 .
AF045655 mRNA. Translation: AAC05671.1 .
AF045656 mRNA. Translation: AAC05672.1 .
PIRi A45769.
RefSeqi NP_989448.1. NM_204117.1. [Q05199-2 ]
UniGenei Gga.135.

3D structure databases

ProteinModelPortali Q05199.
SMRi Q05199. Positions 136-203.
ModBasei Search...
MobiDBi Search...

Proteomic databases

PaxDbi Q05199.
PRIDEi Q05199.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSGALT00000037781 ; ENSGALP00000036986 ; ENSGALG00000015422 . [Q05199-1 ]
GeneIDi 373906.
KEGGi gga:373906.

Organism-specific databases

CTDi 3084.

Phylogenomic databases

eggNOGi NOG47801.
GeneTreei ENSGT00710000106660.
HOGENOMi HOG000273863.
HOVERGENi HBG006531.
InParanoidi Q05199.
KOi K05455.
PhylomeDBi Q05199.

Enzyme and pathway databases

Reactomei REACT_189763. Signaling by ERBB2.
REACT_194392. GRB2 events in ERBB2 signaling.
REACT_194393. SHC1 events in ERBB4 signaling.
REACT_194394. Signaling by ERBB4.
REACT_194410. SHC1 events in ERBB2 signaling.
REACT_196847. PI3K events in ERBB4 signaling.
REACT_196849. PI3K events in ERBB2 signaling.
REACT_197054. Nuclear signaling by ERBB4.
REACT_198076. Constitutive PI3K/AKT Signaling in Cancer.
REACT_244793. PIP3 activates AKT signaling.

Miscellaneous databases

NextBioi 20813438.
PROi Q05199.

Gene expression databases

ExpressionAtlasi Q05199. baseline and differential.

Family and domain databases

Gene3Di 2.60.40.10. 1 hit.
InterProi IPR000742. 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 ]
Pfami PF07679. I-set. 1 hit.
PF02158. Neuregulin. 1 hit.
[Graphical view ]
PRINTSi PR01089. NEUREGULIN.
SMARTi SM00181. EGF. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view ]
PROSITEi PS00022. EGF_1. 1 hit.
PS50026. EGF_3. 1 hit.
PS50835. IG_LIKE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family."
    Falls D.L., Rosen K.M., Corfas G., Lane W.S., Fischbach G.D.
    Cell 72:801-815(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
    Strain: White leghorn.
    Tissue: Brain.
  2. "A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogenesis."
    Yang X., Kuo Y., Devay P., Yu C., Role L.
    Neuron 20:255-270(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
    Tissue: Brain and Spinal cord.

Entry informationi

Entry nameiNRG1_CHICK
AccessioniPrimary (citable) accession number: Q05199
Secondary accession number(s): O73750, O73751, O73752
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: November 26, 2014
This is version 111 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

External Data

Dasty 3