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Q6R891 (NEB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
Neurabin-2
Alternative name(s):
Neurabin-II
Protein phosphatase 1 regulatory subunit 9B
Spinophilin
Gene names
Name:Ppp1r9b
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length817 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration By similarity.

Subunit structure

Possibly exists as a homodimer, homotrimer or a homotetramer. Interacts with F-actin, PPP1CA, neurabin-1, TGN38 and D2 dopamine receptor. Interacts with RGS1, RGS2, RGS4, RGS19 and ADRA1B, ADRA2A, ADRA2B, ADRA2C, CDKN2A, PPP1R2, RASGFR1 and TIAM1. Interacts (via C-terminus) with SPATA13 (via C-terminal tail) By similarity. Interacts with DCLK2. Ref.6

Subcellular location

Cytoplasmcytoskeleton By similarity. Nucleus By similarity. Cell projectiondendritic spine By similarity. Cell junctionsynapse. Cell junctionadherens junction By similarity. Cytoplasm By similarity. Cell membrane By similarity. Cell projectionlamellipodium By similarity. Cell projectionfilopodium By similarity. Cell projectionruffle membrane By similarity. Note: Enriched at synapse and cadherin-based cell-cell adhesion sites. In neurons, both cytosolic and membrane-associated, and highly enriched in the postsynaptic density apposed to exitatory synapses. Colocalizes with PPP1R2 at actin-rich adherens junctions in epithelial cells and in dendritic spines. Accumulates in the lamellipodium, filopodium and ruffle membrane in response to hepatocyte growth factor (HGF) treatment By similarity.

Domain

The PP1 binding region is natively unstructured, upon PP1 binding, it acquires structure, blocks a substrate-binding site, and restricts PP1 phosphatase specificity to a subset of substrates By similarity.

Post-translational modification

Stimulation of D1 (but not D2) dopamine receptors induces Ser-94 phosphorylation. Dephosphorylation of Ser-94 is mediated mainly by PP1 and to a lesser extent by PP2A. Phosphorylation of spinophilin disrupts its association with F-actin, but does not affect its binding to PP1 By similarity.

Sequence similarities

Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Nucleus
Synapse
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   LigandActin-binding
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Traceable author statement PubMed 10922077. Source: MGI

actin filament organization

Inferred from physical interaction PubMed 15996550. Source: MGI

calcium-mediated signaling

Inferred from mutant phenotype PubMed 17464283. Source: MGI

cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to morphine

Inferred from mutant phenotype PubMed 18439408. Source: UniProtKB

dendrite development

Inferred from mutant phenotype PubMed 10922077. Source: MGI

filopodium assembly

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

regulation of opioid receptor signaling pathway

Inferred from mutant phenotype PubMed 18439408. Source: UniProtKB

regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 15218143. Source: MGI

   Cellular_componentadherens junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

cortical actin cytoskeleton

Inferred from direct assay PubMed 15996550. Source: MGI

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine

Inferred from electronic annotation. Source: UniProtKB-SubCell

filopodium

Inferred from direct assay PubMed 15996550. Source: MGI

lamellipodium

Inferred from sequence or structural similarity. Source: UniProtKB

nucleoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle membrane

Inferred from sequence or structural similarity. Source: UniProtKB

synapse

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionactin binding

Traceable author statement PubMed 10922077. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6R891-1)

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: Q6R891-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-424: Missing.
     425-456: YEPESGCVEIPGLSEEEDPAPSRKIHFSTAPI → MDTGLHATQLAQGPSPANVLLPSYGPLRTAPP

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 817817Neurabin-2
PRO_0000228615

Regions

Domain496 – 58489PDZ
Region1 – 154154Actin-binding By similarity
Region100 – 371272Interacts with D(2) dopamine receptor By similarity
Region164 – 282119Actin-binding By similarity
Region169 – 25587Interacts with ADRA2A, ADRA2B and ADRA2C By similarity
Region417 – 49478Interacts with protein phosphatase 1 By similarity
Region480 – 52546Interacts with RGS2 By similarity
Region595 – 816222Interacts with TGN38 By similarity
Coiled coil595 – 61622 Potential
Coiled coil665 – 816152 Potential
Motif575 – 5784PP1-binding motif
Compositional bias253 – 2608Poly-Pro

Amino acid modifications

Modified residue151Phosphoserine; by MAPK1 Ref.5
Modified residue171Phosphoserine; by CDK5 Ref.5
Modified residue941Phosphoserine; by PKA Ref.4
Modified residue1001Phosphoserine By similarity
Modified residue1161Phosphoserine By similarity
Modified residue1921Phosphoserine By similarity
Modified residue2051Phosphoserine; by MAPK1 Ref.5

Natural variations

Alternative sequence1 – 424424Missing in isoform 2.
VSP_017674
Alternative sequence425 – 45632YEPES…STAPI → MDTGLHATQLAQGPSPANVL LPSYGPLRTAPP in isoform 2.
VSP_017675

Experimental info

Mutagenesis151S → E: Increases filopodial density. Ref.5

Sequences

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

Last modified July 5, 2004. Version 1.
Checksum: 1654037C196F2F6B

FASTA81789,520
        10         20         30         40         50         60 
MMKTEPRGPG GPLRSASPHR SAYEAGIQAL KPPDAPGPDE APKAAHHKKY GSNVHRIKSM 

        70         80         90        100        110        120 
FLQMGTTAGP PGEAGGGAGM AEAPRASDRG VRLSLPRASS LNENVDHSAL LKLGTSVSER 

       130        140        150        160        170        180 
VSRFDSKPAP SAQPAPPPHP PSRLQETRKL FERSVPAASG GDKEAVARRL LRQERAGLQD 

       190        200        210        220        230        240 
RKLDVVVRFN GSTEALDKLD ADAVSPTVSQ LSAVFEKADS RTGLHRAPGP PRAAGAPQVN 

       250        260        270        280        290        300 
SKLVTKRSRV FQPPPPPPAP SGDGATEKER GPGGQQPPQH RVAPARPPPK PREVRKIKPV 

       310        320        330        340        350        360 
EVEESGESEA ESAPGEVIQA EVTVHAALEN GSTPATTASP APEEPKAEAV PEEEAAASVA 

       370        380        390        400        410        420 
TLERGVDNGR APDMAPEEVD ESKKEDFSEA DLVDVSAYSG LGEDSGGSAL EEDDEEDEED 

       430        440        450        460        470        480 
GEPPYEPESG CVEIPGLSEE EDPAPSRKIH FSTAPIQVFS TYSNEDYDRR NEDVDPMAAS 

       490        500        510        520        530        540 
AEYELEKRVE RLELFPVELE KDSEGLGISI IGMGAGADMG LEKLGIFVKT VTEGGAAHRD 

       550        560        570        580        590        600 
GRIQVNDLLV EVDGTSLVGV TQSFAASVLR NTKGRVRFMI GRERPGEQSE VAQLIQQTLE 

       610        620        630        640        650        660 
QERWQREMME QRYAQYGEDD EETGEYATDE DEELSPTFPG GEMAIEVFEL AENEDALSPV 

       670        680        690        700        710        720 
EMEPEKLVHK FKELQIKHAV TEAEIQQLKR KLQSLEQEKG RWRVEKAQLE QSVEENKERM 

       730        740        750        760        770        780 
EKLEGYWGEA QSLCQAVDEH LRETQAQYQA LERKYSKAKR LIKDYQQKEI EFLKKETAQR 

       790        800        810 
RVLEESELAR KEEMDKLLDK ISELEGNLQT LRNSNST 

« Hide

Isoform 2 [UniParc].

Checksum: 2CC9E6E92DBC8A80
Show »

FASTA39344,846

References

« Hide 'large scale' references
[1]"Mouse spinophilin cDNA."
Allen P.B.
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: C57BL/6.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"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] (ISOFORM 2).
Tissue: Eye.
[4]"Regulation of spinophilin Ser94 phosphorylation in neostriatal neurons involves both DARPP-32-dependent and independent pathways."
Uematsu K., Futter M., Hsieh-Wilson L.C., Higashi H., Maeda H., Nairn A.C., Greengard P., Nishi A.
J. Neurochem. 95:1642-1652(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PKA, PHOSPHORYLATION AT SER-94, DEPHOSPHORYLATION BY PP1 AND PP2A.
[5]"Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)."
Futter M., Uematsu K., Bullock S.A., Kim Y., Hemmings H.C. Jr., Nishi A., Greengard P., Nairn A.C.
Proc. Natl. Acad. Sci. U.S.A. 102:3489-3494(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY MAPK1 AND CDK5, PHOSPHORYLATION AT SER-15; SER-17 AND SER-205, MUTAGENESIS OF SER-15.
[6]"Common and divergent roles for members of the mouse DCX superfamily."
Coquelle F.M., Levy T., Bergmann S., Wolf S.G., Bar-El D., Sapir T., Brody Y., Orr I., Barkai N., Eichele G., Reiner O.
Cell Cycle 5:976-983(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DCLK2.
[7]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY508450 mRNA. Translation: AAR91608.1.
AL606480 Genomic DNA. Translation: CAI23964.1.
AL606480 Genomic DNA. Translation: CAI23965.1.
BC029672 mRNA. Translation: AAH29672.1.
RefSeqNP_758465.2. NM_172261.3.
UniGeneMm.229087.

3D structure databases

ProteinModelPortalQ6R891.
SMRQ6R891. Positions 424-583.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid229847. 4 interactions.
IntActQ6R891. 7 interactions.
MINTMINT-275541.

PTM databases

PhosphoSiteQ6R891.

Proteomic databases

PaxDbQ6R891.
PRIDEQ6R891.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000038696; ENSMUSP00000041732; ENSMUSG00000038976. [Q6R891-1]
ENSMUST00000107748; ENSMUSP00000103377; ENSMUSG00000038976. [Q6R891-2]
GeneID217124.
KEGGmmu:217124.
UCSCuc007kzr.2. mouse. [Q6R891-1]
uc007kzs.2. mouse. [Q6R891-2]

Organism-specific databases

CTD84687.
MGIMGI:2387581. Ppp1r9b.

Phylogenomic databases

eggNOGNOG314102.
GeneTreeENSGT00390000010033.
HOGENOMHOG000252962.
HOVERGENHBG005213.
InParanoidQ6R891.
KOK17551.
OMAPKAAHHK.
OrthoDBEOG7XM2WV.
PhylomeDBQ6R891.
TreeFamTF105540.

Gene expression databases

BgeeQ6R891.
CleanExMM_PPP1R9B.
GenevestigatorQ6R891.

Family and domain databases

Gene3D2.30.42.10. 1 hit.
InterProIPR001478. PDZ.
[Graphical view]
PfamPF00595. PDZ. 1 hit.
[Graphical view]
SMARTSM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF50156. SSF50156. 1 hit.
PROSITEPS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPP1R9B. mouse.
NextBio375573.
PROQ6R891.
SOURCESearch...

Entry information

Entry nameNEB2_MOUSE
AccessionPrimary (citable) accession number: Q6R891
Secondary accession number(s): Q8K0X7
Entry history
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot