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Protein

PRKCA-binding protein

Gene

Pick1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi44 – 441ZincCurated
Metal bindingi46 – 461ZincCurated

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • Arp2/3 complex binding Source: UniProtKB
  • ATPase activity Source: UniProtKB
  • ephrin receptor binding Source: UniProtKB
  • G-protein coupled glutamate receptor binding Source: UniProtKB
  • G-protein coupled receptor binding Source: UniProtKB
  • GTPase binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein C-terminus binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • protein kinase C binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • receptor tyrosine kinase binding 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
  • receptor clustering Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Actin-binding, Calcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69437. Pick1.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • dendrite Source: RGD
  • Golgi apparatus Source: UniProtKB
  • neuron projection Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: UniProtKB
  • postsynaptic membrane Source: UniProtKB-KW
  • presynaptic membrane Source: UniProtKB
  • protein complex Source: UniProtKB
  • synapse Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi27 – 282KD → AA: Abolishes interaction with other proteins, but not with itself. 4 Publications
Mutagenesisi44 – 441C → G: Decreased lipid membrane binding, but no effect on peptide ligand recognition. 1 Publication
Mutagenesisi46 – 461C → G: Decreased lipid membrane binding, but no effect on peptide ligand recognition. 1 Publication
Mutagenesisi79 – 791K → E: No effect on lipid membrane binding. 1 Publication
Mutagenesisi81 – 811K → E: No effect on lipid membrane binding. 1 Publication
Mutagenesisi251 – 2522KK → 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 Publication
Mutagenesisi413 – 4131W → A: Abolishes association with Arp2/3 complex and the inhibitory function on Arp2/3 complex-mediated actin nucleation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 416416PRKCA-binding proteinPRO_0000058429Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei82 – 821PhosphothreonineBy similarity
Lipidationi414 – 4141S-palmitoyl cysteine; by DHHC8By similarity

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.
PhosphoSiteiQ9EP80.
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

WithEntry#Exp.IntActNotes
Btg2P270493EBI-77728,EBI-78953
Gria2P1949112EBI-77728,EBI-77718
Gria3P194927EBI-77728,EBI-77764
Grm7P354002EBI-77728,EBI-6936416
Grm7Q633372EBI-77728,EBI-6935714

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • Arp2/3 complex binding Source: UniProtKB
  • ephrin receptor binding Source: UniProtKB
  • G-protein coupled glutamate receptor binding Source: UniProtKB
  • G-protein coupled receptor binding Source: UniProtKB
  • GTPase binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • protein kinase C binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • receptor tyrosine kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi250021. 10 interactions.
DIPiDIP-30941N.
IntActiQ9EP80. 10 interactions.
MINTiMINT-86023.
STRINGi10116.ENSRNOP00000016077.

Structurei

Secondary structure

1
416
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi18 – 269Combined sources
Beta strandi35 – 395Combined sources
Beta strandi41 – 433Combined sources
Beta strandi45 – 528Combined sources
Helixi57 – 615Combined sources
Beta strandi69 – 735Combined sources
Beta strandi76 – 783Combined sources
Helixi83 – 9210Combined sources
Beta strandi95 – 10410Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LUINMR-A19-110[»]
2PKUNMR-A18-104[»]
3HPKX-ray2.20A/B1-110[»]
3HPMX-ray2.80A/B19-110[»]
ProteinModelPortaliQ9EP80.
SMRiQ9EP80. Positions 18-104.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9EP80.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 10584PDZPROSITE-ProRule annotationAdd
BLAST
Domaini144 – 357214AHPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi382 – 3898Poly-Glu

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.

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG3651. Eukaryota.
ENOG410YZG6. LUCA.
HOGENOMiHOG000007646.
HOVERGENiHBG053600.
InParanoidiQ9EP80.
PhylomeDBiQ9EP80.

Family and domain databases

Gene3Di1.20.1270.60. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR027267. AH/BAR-dom.
IPR010504. AH_dom.
IPR030798. Arfaptin_fam.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR12141. PTHR12141. 1 hit.
PfamiPF06456. Arfaptin. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]
SMARTiSM01015. Arfaptin. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
PROSITEiPS50870. AH. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti401 – 4022RG → TW in AAK54603 (PubMed:11237868).Curated

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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LUINMR-A19-110[»]
2PKUNMR-A18-104[»]
3HPKX-ray2.20A/B1-110[»]
3HPMX-ray2.80A/B19-110[»]
ProteinModelPortaliQ9EP80.
SMRiQ9EP80. Positions 18-104.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250021. 10 interactions.
DIPiDIP-30941N.
IntActiQ9EP80. 10 interactions.
MINTiMINT-86023.
STRINGi10116.ENSRNOP00000016077.

PTM databases

iPTMnetiQ9EP80.
PhosphoSiteiQ9EP80.
SwissPalmiQ9EP80.

Proteomic databases

PaxDbiQ9EP80.
PRIDEiQ9EP80.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi84591.
KEGGirno:84591.
UCSCiRGD:69437. rat.

Organism-specific databases

CTDi9463.
RGDi69437. Pick1.

Phylogenomic databases

eggNOGiKOG3651. Eukaryota.
ENOG410YZG6. LUCA.
HOGENOMiHOG000007646.
HOVERGENiHBG053600.
InParanoidiQ9EP80.
PhylomeDBiQ9EP80.

Miscellaneous databases

EvolutionaryTraceiQ9EP80.
PROiQ9EP80.

Family and domain databases

Gene3Di1.20.1270.60. 1 hit.
2.30.42.10. 1 hit.
InterProiIPR027267. AH/BAR-dom.
IPR010504. AH_dom.
IPR030798. Arfaptin_fam.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR12141. PTHR12141. 1 hit.
PfamiPF06456. Arfaptin. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]
SMARTiSM01015. Arfaptin. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
PROSITEiPS50870. AH. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPICK1_RAT
AccessioniPrimary (citable) accession number: Q9EP80
Secondary accession number(s): Q546X4, Q925D1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 2, 2002
Last sequence update: March 1, 2001
Last modified: June 8, 2016
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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.