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Q9EP80 (PICK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
PRKCA-binding protein
Alternative name(s):
Protein interacting with C kinase 1
Protein kinase C-alpha-binding protein
Gene names
Name:Pick1
Synonyms:Prkcabp
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length416 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 ACCN3/ACCN2 channel. Ref.9

Subunit structure

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 ACCN1 and ACCN2; 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. Ref.1 Ref.2 Ref.3 Ref.5 Ref.7 Ref.8 Ref.11 Ref.12

Subcellular location

Cytoplasmperinuclear region. Membrane; Peripheral membrane protein. Note: Also membrane-associated, present at excitatory synapses.

Tissue specificity

Ubiquitous.

Developmental stage

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

Post-translational modification

Phosphorylated By similarity.

Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors By similarity.

Sequence similarities

Contains 1 AH domain.

Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
   Cellular componentCytoplasm
Membrane
   LigandCalcium
Metal-binding
Zinc
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological processactivation of protein kinase C activity by G-protein coupled receptor protein signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

dopamine transport

Non-traceable author statement. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.3. Source: UniProtKB

receptor clustering

Inferred from mutant phenotype Ref.1. Source: UniProtKB

   Cellular componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

postsynaptic density

Inferred from direct assay Ref.1. Source: UniProtKB

presynaptic membrane

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex

Inferred from physical interaction Ref.1. Source: UniProtKB

synaptosome

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular functionATPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

G-protein coupled glutamate receptor binding

Traceable author statement. Source: UniProtKB

GTPase binding

Traceable author statement. Source: UniProtKB

ephrin receptor binding

Traceable author statement. Source: UniProtKB

identical protein binding

Inferred from direct assay Ref.1. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein C-terminus binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein domain specific binding

Inferred from mutant phenotype. Source: RGD

protein kinase C binding

Inferred from direct assay. Source: UniProtKB

receptor tyrosine kinase binding

Traceable author statement. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 416416PRKCA-binding protein
PRO_0000058429

Regions

Domain22 – 10584PDZ
Domain144 – 357214AH
Compositional bias382 – 3898Poly-Glu

Sites

Metal binding441Zinc Probable
Metal binding461Zinc Probable

Amino acid modifications

Modified residue181Phosphothreonine By similarity
Modified residue821Phosphothreonine By similarity

Experimental info

Mutagenesis27 – 282KD → AA: Abolishes interaction with other proteins, but not with itself. Ref.1 Ref.2 Ref.6
Mutagenesis441C → G: Decreased lipid membrane binding, but no effect on peptide ligand recognition. Ref.1 Ref.2 Ref.6 Ref.12
Mutagenesis461C → G: Decreased lipid membrane binding, but no effect on peptide ligand recognition. Ref.1 Ref.2 Ref.6 Ref.12
Mutagenesis791K → E: No effect on lipid membrane binding. Ref.1 Ref.2 Ref.6 Ref.12
Mutagenesis811K → E: No effect on lipid membrane binding. Ref.1 Ref.2 Ref.6 Ref.12
Sequence conflict401 – 4022RG → TW in AAK54603. Ref.3

Secondary structure

................. 416
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9EP80 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 8FDE0D78BB26C006

FASTA41646,606
        10         20         30         40         50         60 
MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV QVFDNTPAAL 

        70         80         90        100        110        120 
DGTVAAGDEI TGVNGRSIKG KTKVEVAKMI QEVKGEVTIH YNKLQADPKQ GMSLDIVLKK 

       130        140        150        160        170        180 
VKHRLVENMS SGTADALGLS RAILCNDGLV KRLEELERTA ELYKGMTEHT KNLLRAFYEL 

       190        200        210        220        230        240 
SQTHRAFGDV FSVIGVREPQ PAASEAFVKF ADAHRSIEKF GIRLLKTIKP MLTDLNTYLN 

       250        260        270        280        290        300 
KAIPDTRLTI KKYLDVKFEY LSYCLKVKEM DDEEYSCIAL GEPLYRVSTG NYEYRLILRC 

       310        320        330        340        350        360 
RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRFVST MSKYYNDCYA VLRDADVFPI 

       370        380        390        400        410 
EVDLAHTTLA YGPNQGGFTD GEDEEEEEED GAAREVSKDA RGATGPTDKG GSWCDS 

« Hide

References

[1]"Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1."
Xia J., Zhang X., Staudinger J., Huganir R.L.
Neuron 22:179-187(1999) [PubMed: 10027300] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH GRIA2; GRIA3 AND ISOFORM 4C OF GRIA4, MUTAGENESIS OF 27-LYS-ASP-28.
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"Interaction of the C-terminal tail region of the metabotropic glutamate receptor 7 with the protein kinase C substrate PICK1."
El Far O., Airas J., Wischmeyer E., Nehring R.B., Karschin A., Betz H.
Eur. J. Neurosci. 12:4215-4221(2000) [PubMed: 11122333] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH GRM4; GRM7; GRM8; GRIK3 AND PRKCA, MUTAGENESIS OF 27-LYS-ASP-28.
Tissue: Brain.
[3]"Mitogen-stimulated TIS21 protein interacts with a protein-kinase-Calpha-binding protein rPICK1."
Lin W.-J., Chang Y.-F., Wang W.-L., Huang C.-Y.F.
Biochem. J. 354:635-643(2001) [PubMed: 11237868] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH BTG2.
[4]"Interaction of glutamate transporter GLT1b with PICK1, a protein regulating targeting and trafficking at excitatory synapses."
Chen W., Rosenberg P.A.
Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Brain.
[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: 10340301] [Abstract]
Cited for: INTERACTION WITH GRIA2; GRIA3 AND GRIA4 ISOFORM 4C.
[6]"Molecular determinants for PICK1 synaptic aggregation and mGluR7a receptor coclustering: role of the PDZ, coiled-coil, and acidic domains."
Boudin H., Craig A.M.
J. Biol. Chem. 276:30270-30276(2001) [PubMed: 11375398] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF 27-LYS-ASP-28.
[7]"NSF ATPase and alpha-/beta-SNAPs disassemble the AMPA receptor-PICK1 complex."
Hanley J.G., Khatri L., Hanson P.I., Ziff E.B.
Neuron 34:53-67(2002) [PubMed: 11931741] [Abstract]
Cited for: INTERACTION WITH NAPA AND NAPB.
[8]"Surface expression of the netrin receptor UNC5H1 is regulated through a protein kinase C-interacting protein/protein kinase-dependent mechanism."
Williams M.E., Wu S.C.-Y., McKenna W.L., Hinck L.
J. Neurosci. 23:11279-11288(2003) [PubMed: 14672991] [Abstract]
Cited for: INTERACTION WITH UNC5A.
[9]"PICK1 is a calcium-sensor for NMDA-induced AMPA receptor trafficking."
Hanley J.G., Henley J.M.
EMBO J. 24:3266-3278(2005) [PubMed: 16138078] [Abstract]
Cited for: FUNCTION, CALCIUM-BINDING.
[10]"Zinc binding site in PICK1 is dominantly located at the CPC motif of its PDZ domain."
Shi Y., Zhang L., Yuan J., Xiao H., Yang X., Niu L.
J. Neurochem. 106:1027-1034(2008) [PubMed: 18429931] [Abstract]
Cited for: ZINC-BINDING SITES.
[11]"Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1."
Jo J., Heon S., Kim M.J., Son G.H., Park Y., Henley J.M., Weiss J.L., Sheng M., Collingridge G.L., Cho K.
Neuron 60:1095-1111(2008) [PubMed: 19109914] [Abstract]
Cited for: INTERACTION WITH NCS1.
[12]"Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes."
Pan L., Wu H., Shen C., Shi Y., Jin W., Xia J., Zhang M.
EMBO J. 26:4576-4587(2007) [PubMed: 17914463] [Abstract]
Cited for: STRUCTURE BY NMR OF 18-104 IN COMPLEX WITH GRIA2, INTERACTION WITH GRIA2, MUTAGENESIS OF CYS-44; CYS-46; LYS-79 AND LYS-81.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF327562 mRNA. Translation: AAG48152.1.
AJ240083 mRNA. Translation: CAC17808.2.
AF373289 mRNA. Translation: AAK54603.1.
AF542094 mRNA. Translation: AAO49507.1.
IPIIPI00188758.
RefSeqNP_445912.1. NM_053460.1.
UniGeneRn.24750.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PKUNMR-A18-104[»]
3HPKX-ray2.20A/B1-110[»]
3HPMX-ray2.80A/B19-110[»]
ProteinModelPortalQ9EP80.
SMRQ9EP80. Positions 18-104.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9EP80. 5 interactions.
MINTMINT-86023.
STRINGQ9EP80.

PTM databases

PhosphoSiteQ9EP80.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID84591.
KEGGrno:84591.
UCSCNM_053460. rat.

Organism-specific databases

CTD9463.
RGD69437. Pick1.

Phylogenomic databases

eggNOGroNOG06087.
GeneTreeENSGT00440000033690.
HOVERGENHBG053600.
InParanoidQ9EP80.
OrthoDBEOG4GQQ55.

Gene expression databases

ArrayExpressQ9EP80.
GenevestigatorQ9EP80.
GermOnlineENSRNOG00000011507. Rattus norvegicus.

Family and domain databases

InterProIPR010504. Arfaptin_homology_dom.
IPR001478. PDZ/DHR/GLGF.
[Graphical view]
Gene3DG3DSA:1.20.1270.60. Arfaptin. 1 hit.
PfamPF06456. Arfaptin. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]
SMARTSM01015. Arfaptin. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF50156. PDZ. 1 hit.
PROSITEPS50870. AH. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio617193.

Entry information

Entry namePICK1_RAT
AccessionPrimary (citable) accession number: Q9EP80
Secondary accession number(s): Q546X4, Q925D1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 2, 2002
Last sequence update: March 1, 2001
Last modified: January 25, 2012
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families