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Protein

PRKCA-binding protein

Gene

Pick1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competetive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi44ZincCurated1
Metal bindingi46ZincCurated1

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • Arp2/3 complex binding Source: UniProtKB
  • cytoskeletal protein binding Source: RGD
  • enzyme binding Source: RGD
  • ephrin receptor binding Source: UniProtKB
  • G-protein coupled glutamate receptor binding Source: UniProtKB
  • G-protein coupled receptor binding Source: ParkinsonsUK-UCL
  • GTPase binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • ionotropic glutamate receptor binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein C-terminus binding Source: RGD
  • protein domain specific binding Source: RGD
  • protein kinase C binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB
  • SNAP receptor activity Source: UniProtKB

GO - Biological processi

  • cellular response to decreased oxygen levels Source: UniProtKB
  • cellular response to glucose starvation Source: UniProtKB
  • dendritic spine maintenance Source: UniProtKB
  • dendritic spine organization Source: UniProtKB
  • dopamine transport Source: UniProtKB
  • glial cell development Source: UniProtKB
  • long term synaptic depression Source: UniProtKB
  • monoamine transport Source: UniProtKB
  • negative regulation of Arp2/3 complex-mediated actin nucleation Source: UniProtKB
  • negative regulation of cell death Source: ParkinsonsUK-UCL
  • negative regulation of gene expression Source: ParkinsonsUK-UCL
  • positive regulation of receptor internalization Source: UniProtKB
  • protein kinase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • protein targeting Source: RGD
  • receptor clustering Source: UniProtKB

Keywordsi

Molecular functionActin-binding
LigandCalcium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
PRKCA-binding protein
Alternative name(s):
Protein interacting with C kinase 1
Protein kinase C-alpha-binding protein
Gene namesi
Name:Pick1
Synonyms:Prkcabp
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69437 Pick1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Postsynaptic cell membrane, Synapse, Synaptosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27 – 28KD → AA: Abolishes interaction with other proteins, but not with itself. 4 Publications2
Mutagenesisi44C → G: Decreased lipid membrane binding, but no effect on peptide ligand recognition. 1 Publication1
Mutagenesisi46C → G: Decreased lipid membrane binding, but no effect on peptide ligand recognition. 1 Publication1
Mutagenesisi79K → E: No effect on lipid membrane binding. 1 Publication1
Mutagenesisi81K → E: No effect on lipid membrane binding. 1 Publication1
Mutagenesisi251 – 252KK → EE: Abolishes F-actin binding and the inhibitory function on Arp2/3 complex-mediated actin nucleation, impairs lipid vesicle interaction, no effect on Arp2/3 complex association. 1 Publication2
Mutagenesisi413W → A: Abolishes association with Arp2/3 complex and the inhibitory function on Arp2/3 complex-mediated actin nucleation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000584291 – 416PRKCA-binding proteinAdd BLAST416

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei82PhosphothreonineBy similarity1
Lipidationi414S-palmitoyl cysteine; by DHHC8By similarity1

Post-translational modificationi

Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors.By similarity
Palmitoylation on Cys-414 is essential for long-term synaptic depression (LTD).By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ9EP80
PRIDEiQ9EP80

PTM databases

iPTMnetiQ9EP80
PhosphoSitePlusiQ9EP80
SwissPalmiQ9EP80

Expressioni

Tissue specificityi

Ubiquitous.

Developmental stagei

Expressed early in development (E15), and gradually increases, reaching a peak at around 2 weeks after birth.

Interactioni

Subunit structurei

Monomer and homodimer. Interacts with CXADR. Interacts presynaptically with the glutamate receptors GRIA2, GRIA3, GRIK3, isoform 3 of GRIA4, isoform A of GRM4, GRM7 and GRM8; with NAPA and NAPB; and with BTG2. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with PRKCA; with the amine transporters SLC6A2 and SLC6A3; with the channels ASIC1 and ASIC2; with the GTP-binding proteins ARF1 and ARF3; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; with ERBB2 and through its PDZ domain with the C-terminal tail of PRLHR (By similarity). Interacts with UNC5A. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and associates with the ARP2/3 complex. Interacts (via PDZ domain) with ARF1 (activated); the interaction blocks Arp2/3 complex inhibition.By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • cytoskeletal protein binding Source: RGD
  • enzyme binding Source: RGD
  • ephrin receptor binding Source: UniProtKB
  • G-protein coupled glutamate receptor binding Source: UniProtKB
  • G-protein coupled receptor binding Source: ParkinsonsUK-UCL
  • GTPase binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • ionotropic glutamate receptor binding Source: UniProtKB
  • protein C-terminus binding Source: RGD
  • protein domain specific binding Source: RGD
  • protein kinase C binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB
  • SNAP receptor activity Source: UniProtKB

Protein-protein interaction databases

BioGridi250021, 10 interactors
CORUMiQ9EP80
DIPiDIP-30941N
ELMiQ9EP80
IntActiQ9EP80, 19 interactors
MINTiQ9EP80
STRINGi10116.ENSRNOP00000016077

Structurei

Secondary structure

1416
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi18 – 26Combined sources9
Beta strandi35 – 39Combined sources5
Beta strandi41 – 43Combined sources3
Beta strandi45 – 52Combined sources8
Helixi57 – 61Combined sources5
Beta strandi69 – 73Combined sources5
Beta strandi76 – 78Combined sources3
Helixi83 – 92Combined sources10
Beta strandi95 – 104Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LUINMR-A19-110[»]
2PKUNMR-A18-104[»]
3HPKX-ray2.20A/B1-110[»]
3HPMX-ray2.80A/B19-110[»]
ProteinModelPortaliQ9EP80
SMRiQ9EP80
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9EP80

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 105PDZPROSITE-ProRule annotationAdd BLAST84
Domaini144 – 357AHPROSITE-ProRule annotationAdd BLAST214

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi382 – 389Poly-Glu8

Domaini

The AH domain mediates binding to F-actin.
The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization.

Phylogenomic databases

eggNOGiKOG3651 Eukaryota
ENOG410YZG6 LUCA
HOGENOMiHOG000007646
HOVERGENiHBG053600
InParanoidiQ9EP80
PhylomeDBiQ9EP80

Family and domain databases

CDDicd07659 BAR_PICK1, 1 hit
Gene3Di1.20.1270.60, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR010504 AH_dom
IPR030798 Arfaptin_fam
IPR001478 PDZ
IPR036034 PDZ_sf
IPR037959 PICK1_BAR
PANTHERiPTHR12141 PTHR12141, 1 hit
PfamiView protein in Pfam
PF06456 Arfaptin, 1 hit
PF00595 PDZ, 1 hit
SMARTiView protein in SMART
SM01015 Arfaptin, 1 hit
SM00228 PDZ, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF50156 SSF50156, 1 hit
PROSITEiView protein in PROSITE
PS50870 AH, 1 hit
PS50106 PDZ, 1 hit

Sequencei

Sequence statusi: Complete.

Q9EP80-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV
60 70 80 90 100
QVFDNTPAAL DGTVAAGDEI TGVNGRSIKG KTKVEVAKMI QEVKGEVTIH
110 120 130 140 150
YNKLQADPKQ GMSLDIVLKK VKHRLVENMS SGTADALGLS RAILCNDGLV
160 170 180 190 200
KRLEELERTA ELYKGMTEHT KNLLRAFYEL SQTHRAFGDV FSVIGVREPQ
210 220 230 240 250
PAASEAFVKF ADAHRSIEKF GIRLLKTIKP MLTDLNTYLN KAIPDTRLTI
260 270 280 290 300
KKYLDVKFEY LSYCLKVKEM DDEEYSCIAL GEPLYRVSTG NYEYRLILRC
310 320 330 340 350
RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRFVST MSKYYNDCYA
360 370 380 390 400
VLRDADVFPI EVDLAHTTLA YGPNQGGFTD GEDEEEEEED GAAREVSKDA
410
RGATGPTDKG GSWCDS
Length:416
Mass (Da):46,606
Last modified:March 1, 2001 - v1
Checksum:i8FDE0D78BB26C006
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti401 – 402RG → TW in AAK54603 (PubMed:11237868).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF327562 mRNA Translation: AAG48152.1
AJ240083 mRNA Translation: CAC17808.2
AF373289 mRNA Translation: AAK54603.1
AF542094 mRNA Translation: AAO49507.1
RefSeqiNP_445912.1, NM_053460.1
UniGeneiRn.24750

Genome annotation databases

GeneIDi84591
KEGGirno:84591
UCSCiRGD:69437 rat

Similar proteinsi

Entry informationi

Entry nameiPICK1_RAT
AccessioniPrimary (citable) accession number: Q9EP80
Secondary accession number(s): Q546X4, Q925D1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 2, 2002
Last sequence update: March 1, 2001
Last modified: April 25, 2018
This is version 144 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health