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P43322

- NRG1_RAT

UniProt

P43322 - NRG1_RAT

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Protein

Pro-neuregulin-1, membrane-bound isoform

Gene

Nrg1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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. 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 vessicles 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 By similarity.By similarity

GO - Molecular functioni

  1. ErbB-3 class receptor binding Source: RGD

GO - Biological processi

  1. embryo development Source: InterPro
  2. glucose transport Source: RGD
  3. myelination Source: RGD
  4. regulation of blood pressure Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

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
Glial growth factor
Heregulin
Short name:
HRG
Neu differentiation factor
Sensory and motor neuron-derived factor
Gene namesi
Name:Nrg1
Synonyms:Ndf
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi621341. Nrg1.

Subcellular locationi

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
Propeptidei1 – 13131 PublicationPRO_0000019465Add
BLAST
Chaini14 – 662649Pro-neuregulin-1, membrane-bound isoformPRO_0000019466Add
BLAST
Chaini14 – 264251Neuregulin-1PRO_0000019467Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi57 ↔ 112
Glycosylationi120 – 1201N-linked (GlcNAc...)Sequence Analysis
Glycosylationi126 – 1261N-linked (GlcNAc...)Sequence Analysis
Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi182 ↔ 196By similarity
Disulfide bondi190 ↔ 210By similarity
Disulfide bondi212 ↔ 221By 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.
N- and O-glycosylated By similarity. Extensive glycosylation precedes the proteolytic cleavage.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP43322.
PRIDEiP43322.

PTM databases

PhosphoSiteiP43322.

Expressioni

Tissue specificityi

Widely expressed. Most tissues contain isoform alpha2A and isoform alpha2B. Isoform Alpha2 and isoform beta2 are the predominant forms in mesenchymal and non-neuronal organs. Isoform Beta1 is enriched in brain and spinal cord, but not in muscle and heart. Isoform Alpha2C is highly expressed in spinal cord, moderately in lung, brain, ovary, and stomach, in low amounts in the kidney, skin and heart and not detected in the liver, spleen, and placenta.

Gene expression databases

GenevestigatoriP43322.

Interactioni

Subunit structurei

The cytoplasmic domain interacts with the LIM domain region of LIMK1. Interacts with ERBB3 and ERBB4.1 Publication

Protein-protein interaction databases

MINTiMINT-4996739.

Structurei

3D structure databases

ProteinModelPortaliP43322.
SMRiP43322. Positions 177-225.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini14 – 265252ExtracellularSequence AnalysisAdd
BLAST
Topological domaini289 – 662374CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei266 – 28823Helical; Note=Internal signal sequenceSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini37 – 12892Ig-like C2-typeAdd
BLAST
Domaini178 – 22245EGF-likePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi165 – 17713Ser/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.
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.
HOVERGENiHBG006531.
InParanoidiP43322.
KOiK05455.
PhylomeDBiP43322.

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 (8)i

Sequence statusi: Complete.

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

This entry describes 8 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform Beta4 (identifier: P43322-1) [UniParc]FASTAAdd to Basket

Also known as: NDF42A

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
MSERKEGRGK GKGKKKDRGS RGKPGPAEGD PSPALPPRLK EMKSQESAAG
60 70 80 90 100
SKLVLRCETS SEYSSLRFKW FKNGNELNRK NKPENIKIQK KPGKSELRIN
110 120 130 140 150
KASLADSGEY MCKVISKLGN DSASANITIV ESNEFITGMP ASTETAYVSS
160 170 180 190 200
ESPIRISVST EGANTSSSTS TSTTGTSHLI KCAEKEKTFC VNGGECFTVK
210 220 230 240 250
DLSNPSRYLC KCPNEFTGDR CQNYVMASFY MTSRRKRQET EKPLERKLDH
260 270 280 290 300
SLVKESKAEE LYQKRVLTIT GICIALLVVG IMCVVAYCKT KKQRQKLHDR
310 320 330 340 350
LRQSLRSERS NLVNIANGPH HPNPPPENVQ LVNQYVSKNV ISSEHIVERE
360 370 380 390 400
VETSFSTSHY TSTAHHSTTV TQTPSHSWSN GHTESVISES NSVIMMSSVE
410 420 430 440 450
NSRHSSPAGG PRGRLHGLGG PRDNSFLRHA RETPDSYRDS PHSERYVSAM
460 470 480 490 500
TTPARMSPVD FHTPSSPKSP PSEMSPPVSS MTVSMPSVAV SPFVEEERPL
510 520 530 540 550
LLVTPPRLRE KKYDHHPQQL NSFHHNPAHQ STSLPPSPLR IVEDEEYETT
560 570 580 590 600
QEYESVQEPV KKVTNSRRAK RTKPNGHIAN RLEMDSNTSS VSSNSESETE
610 620 630 640 650
DERVGEDTPF LGIQNPLAAS LEVAPAFRLA ESRTNPAGRF STQEELQARL
660
SSVIANQDPI AV
Length:662
Mass (Da):73,288
Last modified:November 1, 1996 - v1
Checksum:i1C31ABCF2A8EB1D5
GO
Isoform Alpha2A (identifier: P43322-2) [UniParc]FASTAAdd to Basket

Also known as: NDF38

The sequence of this isoform differs from the canonical sequence as follows:
     213-256: PNEFTGDRCQNYVMASFYMTSRRKRQETEKPLERKLDHSLVKES → QPGFTGARCTENVPMKVQTQE

Show »
Length:639
Mass (Da):70,303
Checksum:i2A5A97DFCE065176
GO
Isoform Alpha2B (identifier: P43322-3) [UniParc]FASTAAdd to Basket

Also known as: NDF19

The sequence of this isoform differs from the canonical sequence as follows:
     213-256: PNEFTGDRCQNYVMASFYMTSRRKRQETEKPLERKLDHSLVKES → QPGFTGARCTENVPMKVQTQE
     446-484: YVSAMTTPAR...SPPVSSMTVS → HNLIAELRRN...SSITHLGFIL
     485-662: Missing.

Show »
Length:461
Mass (Da):50,809
Checksum:iBE384394D3C88841
GO
Isoform Alpha2C (identifier: P43322-4) [UniParc]FASTAAdd to Basket

Also known as: NDF44

The sequence of this isoform differs from the canonical sequence as follows:
     213-256: PNEFTGDRCQNYVMASFYMTSRRKRQETEKPLERKLDHSLVKES → QPGFTGARCTENVPMKVQTQE
     446-662: Missing.

Show »
Length:422
Mass (Da):46,309
Checksum:iAD15AECCB42C9C45
GO
Isoform Beta1 (identifier: P43322-5) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     231-257: MTSRRKRQETEKPLERKLDHSLVKESK → KHLGIEFME

Show »
Length:644
Mass (Da):71,081
Checksum:i2382B5DB8682CE17
GO
Isoform Beta2 (identifier: P43322-6) [UniParc]FASTAAdd to Basket

Also known as: NDF40

The sequence of this isoform differs from the canonical sequence as follows:
     231-256: Missing.
     325-330: PPENVQ → RVRTRG

Show »
Length:636
Mass (Da):70,185
Checksum:i2F621966AA232AB9
GO
Isoform BetA2A (identifier: P43322-7) [UniParc]FASTAAdd to Basket

Also known as: NDF22

The sequence of this isoform differs from the canonical sequence as follows:
     231-256: Missing.

Show »
Length:636
Mass (Da):70,123
Checksum:i995A0710F6F48763
GO
Isoform Beta3 (identifier: P43322-8) [UniParc]FASTAAdd to Basket

Also known as: NDF4

The sequence of this isoform differs from the canonical sequence as follows:
     231-241: MTSRRKRQETE → STSTPFLSLPE
     242-662: Missing.

Show »
Length:241
Mass (Da):26,213
Checksum:i556F9540DD94B32B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti90 – 901K → N AA sequence (PubMed:1349853)Curated
Sequence conflicti137 – 1371T → I AA sequence (PubMed:1349853)Curated
Sequence conflicti208 – 2081Y → S AA sequence (PubMed:1349853)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei213 – 25644PNEFT…LVKES → QPGFTGARCTENVPMKVQTQ E in isoform Alpha2A, isoform Alpha2B and isoform Alpha2C. 1 PublicationVSP_003436Add
BLAST
Alternative sequencei231 – 25727MTSRR…VKESK → KHLGIEFME in isoform Beta1. CuratedVSP_003437Add
BLAST
Alternative sequencei231 – 25626Missing in isoform Beta2 and isoform BetA2A. CuratedVSP_003440Add
BLAST
Alternative sequencei231 – 24111MTSRRKRQETE → STSTPFLSLPE in isoform Beta3. CuratedVSP_003438Add
BLAST
Alternative sequencei242 – 662421Missing in isoform Beta3. CuratedVSP_003439Add
BLAST
Alternative sequencei325 – 3306PPENVQ → RVRTRG in isoform Beta2. CuratedVSP_003441
Alternative sequencei446 – 662217Missing in isoform Alpha2C. 1 PublicationVSP_003442Add
BLAST
Alternative sequencei446 – 48439YVSAM…SMTVS → HNLIAELRRNKAYRSKCMQI QLSATHLRPSSITHLGFIL in isoform Alpha2B. CuratedVSP_003443Add
BLAST
Alternative sequencei485 – 662178Missing in isoform Alpha2B. CuratedVSP_003444Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U02315 mRNA. Translation: AAA19940.1.
U02316 mRNA. Translation: AAA19941.1.
U02317 mRNA. Translation: AAA19942.1.
U02318 mRNA. Translation: AAA19943.1.
U02319 mRNA. Translation: AAA19944.1.
U02320 mRNA. Translation: AAA19945.1.
U02321 mRNA. Translation: AAA19946.1.
U02322 mRNA. Translation: AAA19947.1.
U02323 mRNA. Translation: AAA19948.1.
U02324 mRNA. Translation: AAA19949.1.
M92430 mRNA. No translation available.
PIRiI61718.
I61719.
I61722.
RefSeqiNP_001258052.1. NM_001271123.1. [P43322-8]
UniGeneiRn.37438.

Genome annotation databases

GeneIDi112400.
KEGGirno:112400.
UCSCiRGD:621341. rat. [P43322-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U02315 mRNA. Translation: AAA19940.1 .
U02316 mRNA. Translation: AAA19941.1 .
U02317 mRNA. Translation: AAA19942.1 .
U02318 mRNA. Translation: AAA19943.1 .
U02319 mRNA. Translation: AAA19944.1 .
U02320 mRNA. Translation: AAA19945.1 .
U02321 mRNA. Translation: AAA19946.1 .
U02322 mRNA. Translation: AAA19947.1 .
U02323 mRNA. Translation: AAA19948.1 .
U02324 mRNA. Translation: AAA19949.1 .
M92430 mRNA. No translation available.
PIRi I61718.
I61719.
I61722.
RefSeqi NP_001258052.1. NM_001271123.1. [P43322-8 ]
UniGenei Rn.37438.

3D structure databases

ProteinModelPortali P43322.
SMRi P43322. Positions 177-225.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

MINTi MINT-4996739.

PTM databases

PhosphoSitei P43322.

Proteomic databases

PaxDbi P43322.
PRIDEi P43322.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 112400.
KEGGi rno:112400.
UCSCi RGD:621341. rat. [P43322-1 ]

Organism-specific databases

CTDi 3084.
RGDi 621341. Nrg1.

Phylogenomic databases

eggNOGi NOG47801.
HOVERGENi HBG006531.
InParanoidi P43322.
KOi K05455.
PhylomeDBi P43322.

Miscellaneous databases

NextBioi 617943.

Gene expression databases

Genevestigatori P43322.

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

« Hide 'large scale' publications
  1. "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], ALTERNATIVE SPLICING.
    Tissue: Fibroblast.
  2. "Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit."
    Wen D., Peles E., Cupples R., Suggs S.V., Bacus S.S., Luo Y., Trail G., Hu S., Silbiger S.M., Levy R.B., Koski R.A., Lu H.S., Yarden Y.
    Cell 69:559-572(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA2C), PARTIAL PROTEIN SEQUENCE.
    Tissue: Fibroblast.
  3. "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: PROTEIN SEQUENCE OF 14-36.
  4. "Release of the neuregulin functional polypeptide requires its cytoplasmic tail."
    Liu X., Hwang H., Cao L., Wen D., Liu N., Graham R.M., Zhou M.
    J. Biol. Chem. 273:34335-34340(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION OF PROCESSING (ISOFORM ALPHA2C).
  5. "Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition."
    Wang J.Y., Frenzel K.E., Wen D., Falls D.L.
    J. Biol. Chem. 273:20525-20534(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LIMK1.
  6. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
    Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
    Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "Stimulated ErbB4 internalization is necessary for neuregulin signaling in neurons."
    Liu Y., Tao Y.M., Woo R.S., Xiong W.C., Mei L.
    Biochem. Biophys. Res. Commun. 354:505-510(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiNRG1_RAT
AccessioniPrimary (citable) accession number: P43322
Secondary accession number(s): P43323
, P43324, P43325, P43326, P43327, P43328
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: October 29, 2014
This is version 129 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