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Protein

Neurabin-2

Gene

PPP1R9B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

GO - Molecular functioni

  • actin filament binding Source: GO_Central
  • protein phosphatase 1 binding Source: UniProtKB
  • protein phosphatase inhibitor activity Source: UniProtKB

GO - Biological processi

  • actin filament organization Source: GO_Central
  • calcium-mediated signaling Source: GO_Central
  • cell cycle arrest Source: UniProtKB
  • cell migration Source: UniProtKB
  • cellular response to morphine Source: UniProtKB
  • filopodium assembly Source: UniProtKB
  • modulation of synaptic transmission Source: InterPro
  • negative regulation of cell growth Source: UniProtKB
  • neuron projection development Source: GO_Central
  • regulation of cell growth by extracellular stimulus Source: UniProtKB
  • regulation of cell proliferation Source: UniProtKB
  • regulation of exit from mitosis Source: UniProtKB
  • regulation of opioid receptor signaling pathway Source: UniProtKB
  • RNA splicing Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Keywords - Ligandi

Actin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108819-MONOMER.
SignaLinkiQ96SB3.
SIGNORiQ96SB3.

Names & Taxonomyi

Protein namesi
Recommended name:
Neurabin-2
Alternative name(s):
Neurabin-II
Protein phosphatase 1 regulatory subunit 9B
Spinophilin
Gene namesi
Name:PPP1R9B
Synonyms:PPP1R6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:9298. PPP1R9B.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: GO_Central
  • adherens junction Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • dendrite Source: GO_Central
  • dendritic spine Source: UniProtKB-SubCell
  • filopodium Source: UniProtKB
  • lamellipodium Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: GO_Central
  • protein phosphatase type 1 complex Source: UniProtKB
  • ruffle membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus, Synapse

Pathology & Biotechi

Organism-specific databases

DisGeNETi84687.
PharmGKBiPA33662.

Polymorphism and mutation databases

BioMutaiPPP1R9B.
DMDMi90101416.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002286141 – 815Neurabin-2Add BLAST815

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei15PhosphoserineBy similarity1
Modified residuei17PhosphoserineBy similarity1
Modified residuei94PhosphoserineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei116PhosphoserineBy similarity1
Modified residuei190PhosphoserineCombined sources1
Modified residuei191PhosphothreonineCombined sources1
Modified residuei203PhosphoserineCombined sources1
Modified residuei205PhosphothreonineCombined sources1
Modified residuei436PhosphoserineCombined sources1
Modified residuei656PhosphoserineCombined sources1

Post-translational modificationi

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).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96SB3.
MaxQBiQ96SB3.
PeptideAtlasiQ96SB3.
PRIDEiQ96SB3.

PTM databases

iPTMnetiQ96SB3.
PhosphoSitePlusiQ96SB3.

Expressioni

Gene expression databases

BgeeiENSG00000108819.
CleanExiHS_PPP1R9B.

Interactioni

Subunit structurei

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). Interacts with ADRA2B.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PPP1CAP621365EBI-351275,EBI-357253

GO - Molecular functioni

  • actin filament binding Source: GO_Central
  • protein phosphatase 1 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi124202. 39 interactors.
IntActiQ96SB3. 33 interactors.
MINTiMINT-193423.

Structurei

3D structure databases

ProteinModelPortaliQ96SB3.
SMRiQ96SB3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini494 – 582PDZPROSITE-ProRule annotationAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 154Actin-bindingBy similarityAdd BLAST154
Regioni100 – 369Interaction with D(2) dopamine receptorBy similarityAdd BLAST270
Regioni163 – 281Actin-bindingBy similarityAdd BLAST119
Regioni167 – 253Interaction with ADRA2A, ADRA2B and ADRA2CBy similarityAdd BLAST87
Regioni415 – 492Interaction with protein phosphatase 1By similarityAdd BLAST78
Regioni478 – 523Interaction with RGS2By similarityAdd BLAST46
Regioni593 – 814Interaction with TGN38By similarityAdd BLAST222

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili593 – 614Sequence analysisAdd BLAST22
Coiled coili663 – 814Sequence analysisAdd BLAST152

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi445 – 449PP1-binding motifBy similarity5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi251 – 259Poly-Pro9

Domaini

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

Sequence similaritiesi

Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

HOVERGENiHBG005213.
InParanoidiQ96SB3.
KOiK17551.
PhylomeDBiQ96SB3.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
InterProiIPR029921. NEB2.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR16154:SF24. PTHR16154:SF24. 1 hit.
PfamiPF00595. PDZ. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q96SB3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMKTEPRGPG GPLRSASPHR SAYEAGIQAL KPPDAPGPDE APKGAHHKKY
60 70 80 90 100
GSNVHRIKSM FLQMGTTAGP SGEAGGGAGL AEAPRASERG VRLSLPRASS
110 120 130 140 150
LNENVDHSAL LKLGTSVSER VSRFDSKPAP SAQPAPPPHP PSRLQETRKL
160 170 180 190 200
FERSAPAAGG DKEAARRLLR QERAGLQDRK LDVVVRFNGS TEALDKLDAD
210 220 230 240 250
AVSPTVSQLS AVFEKADSRT GLHRGPGLPR AAGVPQVNSK LVSKRSRVFQ
260 270 280 290 300
PPPPPPPAPS GDAPAEKERC PAGQQPPQHR VAPARPPPKP REVRKIKPVE
310 320 330 340 350
VEESGESEAE SAPGEVIQAE VTVHAALENG STVATAASPA PEEPKAQAAP
360 370 380 390 400
EKEAAAVAPP ERGVGNGRAP DVAPEEVDES KKEDFSEADL VDVSAYSGLG
410 420 430 440 450
EDSAGSALEE DDEDDEEDGE PPYEPESGCV EIPGLSEEED PAPSRKIHFS
460 470 480 490 500
TAPIQVFSTY SNEDYDRRNE DVDPMAASAE YELEKRVERL ELFPVELEKD
510 520 530 540 550
SEGLGISIIG MGAGADMGLE KLGIFVKTVT EGGAAHRDGR IQVNDLLVEV
560 570 580 590 600
DGTSLVGVTQ SFAASVLRNT KGRVRFMIGR ERPGEQSEVA QLIQQTLEQE
610 620 630 640 650
RWQREMMEQR YAQYGEDDEE TGEYATDEDE ELSPTFPGGE MAIEVFELAE
660 670 680 690 700
NEDALSPVDM EPEKLVHKFK ELQIKHAVTE AEIQQLKRKL QSLEQEKGRW
710 720 730 740 750
RVEKAQLEQS VEENKERMEK LEGYWGEAQS LCQAVDEHLR ETQAQYQALE
760 770 780 790 800
RKYSKAKRLI KDYQQKEIEF LKKETAQRRV LEESELARKE EMDKLLDKIS
810
ELEGNLQTLR NSNST
Length:815
Mass (Da):89,192
Last modified:March 21, 2006 - v2
Checksum:iD004CAA7030D3267
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti574V → VRC in CAC37685 (PubMed:11278317).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059776199A → T.Corresponds to variant rs8079707dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ401189 mRNA. Translation: CAC37685.1.
AL713642 mRNA. Translation: CAD28455.2.
RefSeqiNP_115984.3. NM_032595.4.
UniGeneiHs.514323.

Genome annotation databases

EnsembliENST00000316878; ENSP00000475417; ENSG00000108819.
GeneIDi84687.
KEGGihsa:84687.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ401189 mRNA. Translation: CAC37685.1.
AL713642 mRNA. Translation: CAD28455.2.
RefSeqiNP_115984.3. NM_032595.4.
UniGeneiHs.514323.

3D structure databases

ProteinModelPortaliQ96SB3.
SMRiQ96SB3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124202. 39 interactors.
IntActiQ96SB3. 33 interactors.
MINTiMINT-193423.

PTM databases

iPTMnetiQ96SB3.
PhosphoSitePlusiQ96SB3.

Polymorphism and mutation databases

BioMutaiPPP1R9B.
DMDMi90101416.

Proteomic databases

EPDiQ96SB3.
MaxQBiQ96SB3.
PeptideAtlasiQ96SB3.
PRIDEiQ96SB3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316878; ENSP00000475417; ENSG00000108819.
GeneIDi84687.
KEGGihsa:84687.

Organism-specific databases

CTDi84687.
DisGeNETi84687.
GeneCardsiPPP1R9B.
H-InvDBHIX0202435.
HGNCiHGNC:9298. PPP1R9B.
MIMi603325. gene.
neXtProtiNX_Q96SB3.
PharmGKBiPA33662.
GenAtlasiSearch...

Phylogenomic databases

HOVERGENiHBG005213.
InParanoidiQ96SB3.
KOiK17551.
PhylomeDBiQ96SB3.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108819-MONOMER.
SignaLinkiQ96SB3.
SIGNORiQ96SB3.

Miscellaneous databases

ChiTaRSiPPP1R9B. human.
GeneWikiiPPP1R9B.
GenomeRNAii84687.
PROiQ96SB3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108819.
CleanExiHS_PPP1R9B.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
InterProiIPR029921. NEB2.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR16154:SF24. PTHR16154:SF24. 1 hit.
PfamiPF00595. PDZ. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNEB2_HUMAN
AccessioniPrimary (citable) accession number: Q96SB3
Secondary accession number(s): Q8TCR9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 21, 2006
Last modified: November 2, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.