Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

PRKCA-binding protein

Gene

Pick1

Organism
Mus musculus (Mouse)
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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi44 – 441ZincBy similarity
Metal bindingi46 – 461ZincBy similarity

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • Arp2/3 complex binding Source: UniProtKB
  • ATPase activity Source: UniProtKB
  • enzyme binding Source: MGI
  • G-protein coupled receptor binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: ParkinsonsUK-UCL
  • metal ion binding Source: UniProtKB-KW
  • protein C-terminus binding Source: UniProtKB
  • protein domain specific binding Source: ParkinsonsUK-UCL
  • protein kinase C binding Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:894645. Pick1.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB
  • mitochondrion Source: MGI
  • neuronal postsynaptic density Source: MGI
  • neuron projection Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic membrane Source: UniProtKB-KW
  • presynaptic membrane 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. Partial loss of the ASIC1/ASIC3 channel regulation by PKC. 2 Publications
Mutagenesisi27 – 271K → A: Does not abolish the interaction with PKCA. 2 Publications
Mutagenesisi414 – 4141C → S: Fails to rescue cerebellar LTD in PICK1 knockouts. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 416416PRKCA-binding proteinPRO_0000058428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei82 – 821PhosphothreonineBy similarity
Lipidationi414 – 4141S-palmitoyl cysteine; by DHHC81 Publication

Post-translational modificationi

Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors (By similarity). Phosphorylated on tyrosine residues by EPHB2 and on serine or threonine residues by PKC.By similarity2 Publications
Palmitoylation on Cys-414 is essential for long-term synaptic depression (LTD).1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiQ62083.
MaxQBiQ62083.
PaxDbiQ62083.
PRIDEiQ62083.

PTM databases

PhosphoSiteiQ62083.
SwissPalmiQ62083.

Expressioni

Tissue specificityi

Expressed in all tissues examined, with highest levels in brain and testes and lowest levels in lung.

Gene expression databases

CleanExiMM_PICK1.

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. 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.5 Publications

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-283N.
IntActiQ62083. 4 interactions.
MINTiMINT-223505.
STRINGi10090.ENSMUSP00000018295.

Structurei

3D structure databases

ProteinModelPortaliQ62083.
SMRiQ62083. Positions 14-110, 159-345.
ModBaseiSearch...
MobiDBiSearch...

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.By similarity
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 (By similarity).By similarity

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.
InParanoidiQ62083.

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.

Q62083-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV
60 70 80 90 100
QVFDNTPAAL DGTVAAGDEI TGVNGKSIKG 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 DDEEYSCIGP RRALYRVSTG NYEYRLILRC
310 320 330 340 350
RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRFVST MSKYYNDCYA
360 370 380 390 400
VLQDADVFPI EVDLAHTTLA YGPNQGSFTD GEEEDEEEED GAAREVSKDA
410
CGATGPTDKG GSWCDS
Length:416
Mass (Da):46,597
Last modified:July 27, 2011 - v2
Checksum:i437369D0AB7DCE7B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti179 – 1802EL → DV in CAA86675 (PubMed:7844141).Curated
Sequence conflicti198 – 1992EP → DA in CAA86675 (PubMed:7844141).Curated
Sequence conflicti279 – 2802GP → AA in CAA86675 (PubMed:7844141).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46720 mRNA. Translation: CAA86675.1.
AL591913 Genomic DNA. No translation available.
AL591921 Genomic DNA. No translation available.
CCDSiCCDS27635.1.
PIRiA56486.
UniGeneiMm.259464.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46720 mRNA. Translation: CAA86675.1.
AL591913 Genomic DNA. No translation available.
AL591921 Genomic DNA. No translation available.
CCDSiCCDS27635.1.
PIRiA56486.
UniGeneiMm.259464.

3D structure databases

ProteinModelPortaliQ62083.
SMRiQ62083. Positions 14-110, 159-345.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-283N.
IntActiQ62083. 4 interactions.
MINTiMINT-223505.
STRINGi10090.ENSMUSP00000018295.

PTM databases

PhosphoSiteiQ62083.
SwissPalmiQ62083.

Proteomic databases

EPDiQ62083.
MaxQBiQ62083.
PaxDbiQ62083.
PRIDEiQ62083.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:894645. Pick1.

Phylogenomic databases

eggNOGiKOG3651. Eukaryota.
ENOG410YZG6. LUCA.
HOGENOMiHOG000007646.
HOVERGENiHBG053600.
InParanoidiQ62083.

Miscellaneous databases

ChiTaRSiPick1. mouse.
PROiQ62083.
SOURCEiSearch...

Gene expression databases

CleanExiMM_PICK1.

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...

Publicationsi

« Hide 'large scale' publications
  1. "PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system."
    Staudinger J., Zhou J., Burgess R., Elledge S.J., Olson E.N.
    J. Cell Biol. 128:263-271(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PRKCA, PHOSPHORYLATION.
    Tissue: T-cell.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha."
    Staudinger J., Lu J., Olson E.N.
    J. Biol. Chem. 272:32019-32024(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: HOMODIMERIZATION, MUTAGENESIS OF LYS-27 AND 27-LYS-ASP-28.
  4. "PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands."
    Torres R., Firestein B.L., Dong H., Staudinger J., Olson E.N., Huganir R.L., Bredt D.S., Gale N.W., Yancopoulos G.D.
    Neuron 21:1453-1463(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPHA7; EPHB1 AND EPHB2, PHOSPHORYLATION.
  5. "The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits."
    Dev K.K., Nishimune A., Henley J.M., Nakanishi S.
    Neuropharmacology 38:635-644(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GRIA2 ISOFORM 1.
  6. "The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins."
    Jaulin-Bastard F., Saito H., Le Bivic A., Ollendorff V., Marchetto S., Birnbaum D., Borg J.-P.
    J. Biol. Chem. 276:15256-15263(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ERBB2.
  7. "PICK1 is required for the control of synaptic transmission by the metabotropic glutamate receptor 7."
    Perroy J., El Far O., Bertaso F., Pin J.P., Betz H., Bockaert J., Fagni L.
    EMBO J. 21:2990-2999(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GRM7.
  8. "ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1."
    Deval E., Salinas M., Baron A., Lingueglia E., Lazdunski M.
    J. Biol. Chem. 279:19531-19539(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF LYS-27 AND 27-LYS-ASP-28, FUNCTION.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain and Testis.
  10. "PICK1 regulates incorporation of calcium-permeable AMPA receptors during cortical synaptic strengthening."
    Clem R.L., Anggono V., Huganir R.L.
    J. Neurosci. 30:6360-6366(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression."
    Thomas G.M., Hayashi T., Huganir R.L., Linden D.J.
    J. Neurosci. 33:15401-15407(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-414, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-414.

Entry informationi

Entry nameiPICK1_MOUSE
AccessioniPrimary (citable) accession number: Q62083
Secondary accession number(s): E9PY04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 2, 2002
Last sequence update: July 27, 2011
Last modified: May 11, 2016
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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