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Q96SB3 (NEB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·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
Synonyms:PPP1R6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length815 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 By similarity. Required for hepatocyte growth factor (HGF)-induced cell migration. Ref.5

Subunit structure

Interacts with DCLK2 By similarity. 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). Ref.1 Ref.5

Subcellular location

Cytoplasmcytoskeleton By similarity. Nucleus By similarity. Cell projectiondendritic spine By similarity. Cell junctionsynapse. Cell junctionadherens junction By similarity. Cytoplasm. Cell membrane. Cell projectionlamellipodium. Cell projectionfilopodium. Cell projectionruffle membrane. 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 By similarity. Accumulates in the lamellipodium, filopodium and ruffle membrane in response to hepatocyte growth factor (HGF) treatment. Ref.1 Ref.5

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 diversityPolymorphism
   DomainCoiled coil
   LigandActin-binding
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Non-traceable author statement Ref.1. Source: UniProtKB

actin filament organization

Inferred from electronic annotation. Source: Ensembl

calcium-mediated signaling

Inferred from electronic annotation. Source: Ensembl

cell cycle arrest

Traceable author statement Ref.1. Source: UniProtKB

cell migration

Inferred from mutant phenotype Ref.5. Source: UniProtKB

cellular response to morphine

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite development

Inferred from electronic annotation. Source: Ensembl

filopodium assembly

Inferred from mutant phenotype Ref.5. Source: UniProtKB

negative regulation of catalytic activity

Non-traceable author statement Ref.1. Source: GOC

negative regulation of cell growth

Inferred from direct assay Ref.1. Source: UniProtKB

regulation of cell growth by extracellular stimulus

Traceable author statement Ref.1. Source: UniProtKB

regulation of cell proliferation

Non-traceable author statement Ref.1. Source: UniProtKB

regulation of exit from mitosis

Non-traceable author statement Ref.1. Source: UniProtKB

regulation of opioid receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentadherens junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

cortical actin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.1Ref.5. Source: UniProtKB

dendritic spine

Inferred from electronic annotation. Source: UniProtKB-SubCell

filopodium

Inferred from direct assay Ref.5. Source: UniProtKB

lamellipodium

Inferred from direct assay Ref.5. Source: UniProtKB

nucleoplasm

Inferred from mutant phenotype Ref.1. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.5. Source: UniProtKB

protein phosphatase type 1 complex

Traceable author statement Ref.1. Source: UniProtKB

ruffle membrane

Inferred from direct assay Ref.5. Source: UniProtKB

synapse

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein phosphatase 1 binding

Non-traceable author statement Ref.1. Source: UniProtKB

protein phosphatase inhibitor activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PPP1CAP621365EBI-351275,EBI-357253

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 815815Neurabin-2
PRO_0000228614

Regions

Domain494 – 58289PDZ
Region1 – 154154Actin-binding By similarity
Region100 – 369270Interacts with D(2) dopamine receptor By similarity
Region163 – 281119Actin-binding By similarity
Region167 – 25387Interacts with ADRA2A, ADRA2B and ADRA2C By similarity
Region415 – 49278Interacts with protein phosphatase 1 By similarity
Region478 – 52346Interacts with RGS2 By similarity
Region593 – 814222Interacts with TGN38 By similarity
Coiled coil593 – 61422 Potential
Coiled coil663 – 814152 Potential
Motif573 – 5764PP1-binding motif
Compositional bias251 – 2599Poly-Pro

Amino acid modifications

Modified residue151Phosphoserine By similarity
Modified residue171Phosphoserine By similarity
Modified residue941Phosphoserine By similarity
Modified residue1001Phosphoserine By similarity
Modified residue1161Phosphoserine By similarity
Modified residue1901Phosphoserine Ref.8
Modified residue2031Phosphoserine Ref.3 Ref.6 Ref.7

Natural variations

Natural variant1991A → T.
Corresponds to variant rs8079707 [ dbSNP | Ensembl ].
VAR_059776

Experimental info

Sequence conflict5741V → VRC in CAC37685. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q96SB3 [UniParc].

Last modified March 21, 2006. Version 2.
Checksum: D004CAA7030D3267

FASTA81589,192
        10         20         30         40         50         60 
MMKTEPRGPG GPLRSASPHR SAYEAGIQAL KPPDAPGPDE APKGAHHKKY GSNVHRIKSM 

        70         80         90        100        110        120 
FLQMGTTAGP SGEAGGGAGL AEAPRASERG VRLSLPRASS LNENVDHSAL LKLGTSVSER 

       130        140        150        160        170        180 
VSRFDSKPAP SAQPAPPPHP PSRLQETRKL FERSAPAAGG DKEAARRLLR QERAGLQDRK 

       190        200        210        220        230        240 
LDVVVRFNGS TEALDKLDAD AVSPTVSQLS AVFEKADSRT GLHRGPGLPR AAGVPQVNSK 

       250        260        270        280        290        300 
LVSKRSRVFQ PPPPPPPAPS GDAPAEKERC PAGQQPPQHR VAPARPPPKP REVRKIKPVE 

       310        320        330        340        350        360 
VEESGESEAE SAPGEVIQAE VTVHAALENG STVATAASPA PEEPKAQAAP EKEAAAVAPP 

       370        380        390        400        410        420 
ERGVGNGRAP DVAPEEVDES KKEDFSEADL VDVSAYSGLG EDSAGSALEE DDEDDEEDGE 

       430        440        450        460        470        480 
PPYEPESGCV EIPGLSEEED PAPSRKIHFS TAPIQVFSTY SNEDYDRRNE DVDPMAASAE 

       490        500        510        520        530        540 
YELEKRVERL ELFPVELEKD SEGLGISIIG MGAGADMGLE KLGIFVKTVT EGGAAHRDGR 

       550        560        570        580        590        600 
IQVNDLLVEV DGTSLVGVTQ SFAASVLRNT KGRVRFMIGR ERPGEQSEVA QLIQQTLEQE 

       610        620        630        640        650        660 
RWQREMMEQR YAQYGEDDEE TGEYATDEDE ELSPTFPGGE MAIEVFELAE NEDALSPVDM 

       670        680        690        700        710        720 
EPEKLVHKFK ELQIKHAVTE AEIQQLKRKL QSLEQEKGRW RVEKAQLEQS VEENKERMEK 

       730        740        750        760        770        780 
LEGYWGEAQS LCQAVDEHLR ETQAQYQALE RKYSKAKRLI KDYQQKEIEF LKKETAQRRV 

       790        800        810 
LEESELARKE EMDKLLDKIS ELEGNLQTLR NSNST 

« Hide

References

« Hide 'large scale' references
[1]"The human tumor suppressor ARF interacts with spinophilin/neurabin II, a type 1 protein-phosphatase-binding protein."
Vivo M., Calogero R.A., Sansone F., Calabro V., Parisi T., Borrelli L., Saviozzi S., La Mantia G.
J. Biol. Chem. 276:14161-14169(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH CDKN2A.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 396-815.
Tissue: Amygdala.
[3]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[4]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[5]"Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration."
Sagara M., Kawasaki Y., Iemura S.I., Natsume T., Takai Y., Akiyama T.
Oncogene 28:1357-1365(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SPATA13.
[6]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[7]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-190, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ401189 mRNA. Translation: CAC37685.1.
AL713642 mRNA. Translation: CAD28455.2.
UniGeneHs.514323.

3D structure databases

ProteinModelPortalQ96SB3.
SMRQ96SB3. Positions 422-581.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124202. 19 interactions.
IntActQ96SB3. 17 interactions.
MINTMINT-193423.
STRING9606.ENSP00000320510.

PTM databases

PhosphoSiteQ96SB3.

Polymorphism databases

DMDM90101416.

Proteomic databases

PaxDbQ96SB3.
PRIDEQ96SB3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316878; ENSP00000475417; ENSG00000108819.
KEGGhsa:84687.

Organism-specific databases

CTD84687.
GeneCardsGC17M048211.
H-InvDBHIX0202435.
HGNCHGNC:9298. PPP1R9B.
MIM603325. gene.
neXtProtNX_Q96SB3.
PharmGKBPA33662.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG314102.
HOVERGENHBG005213.
InParanoidQ96SB3.
KOK17551.
PhylomeDBQ96SB3.

Enzyme and pathway databases

SignaLinkQ96SB3.

Gene expression databases

CleanExHS_PPP1R9B.
GenevestigatorQ96SB3.

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. human.
GeneWikiPPP1R9B.
GenomeRNAi84687.
NextBio74732.
PROQ96SB3.
SOURCESearch...

Entry information

Entry nameNEB2_HUMAN
AccessionPrimary (citable) accession number: Q96SB3
Secondary accession number(s): Q8TCR9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 21, 2006
Last modified: April 16, 2014
This is version 101 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM