Reviewed, UniProtKB/Swiss-Prot Q9EP80 (PICK1_RAT)

Names and origin

Protein names

Recommended name:
    PRKCA-binding protein
Alternative name(s):
    Protein kinase C-alpha-binding protein
    Protein interacting with C kinase 1

Gene names

Name:	Pick1
Synonyms:	Prkcabp

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. May be regulated upon PRKCA activation. May regulate ACCN3/ACCN2 channel.
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.
Subcellular location	Cytoplasm › perinuclear 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.
Sequence similarities	Contains 1 AH domain. Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	activation 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 amino acid phosphorylation Ref.3 Inferred from direct assay. Source: UniProtKB receptor clustering Ref.1 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB dendrite Inferred from direct assay. Source: RGD perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB postsynaptic density Ref.1 Inferred from direct assay. Source: UniProtKB presynaptic membrane Inferred from sequence or structural similarity. Source: UniProtKB protein complex Ref.1 Inferred from physical interaction. Source: UniProtKB synaptosome Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	ATPase activity Inferred from sequence or structural similarity. Source: UniProtKB GTPase binding Traceable author statement. Source: UniProtKB ephrin receptor binding Traceable author statement. Source: UniProtKB identical protein binding Ref.1 Inferred from direct assay. Source: UniProtKB metabotropic glutamate receptor binding Traceable author statement. Source: UniProtKB 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

With	Entry	#Exp.	IntAct	Notes
Btg2	P27049	2	EBI-77728,EBI-78953
Gria2	P19491	6	EBI-77728,EBI-77718
Gria3	P19492	4	EBI-77728,EBI-77764

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 416

416

PRKCA-binding protein

PRO_0000058429

Regions

Domain

22 – 105

84

PDZ

Domain

144 – 357

214

AH

Compositional bias

382 – 389

8

Poly-Glu

Experimental info

Mutagenesis

27 – 28

2

KD → AA: Abolishes interaction with other proteins, but not with itself. Ref.1 Ref.2 Ref.6

Sequence conflict

401 – 402

2

RG → TW in AAK54603. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

416

Helix Strand Turn

Details...

Beta strand

19 – 26

8

Beta strand

35 – 38

4

Beta strand

41 – 43

3

Beta strand

48 – 52

5

Helix

57 – 61

5

Beta strand

69 – 73

5

Helix

83 – 92

10

Beta strand

95 – 103

9

Sequences

	Sequence		Length	Mass (Da)
	Q9EP80-1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 8FDE0D78BB26C006	FASTA	416	46,606
	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

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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF327562 mRNA. Translation: AAG48152.1.
AJ240083 mRNA. Translation: CAC17808.2.
AF373289 mRNA. Translation: AAK54603.1.
AF542094 mRNA. Translation: AAO49507.1.

IPI

IPI00188758.

RefSeq

NP_445912.1.

UniGene

Rn.24750

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2PKU	NMR	-	A	18-104	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9EP80. 4 interactions.

Genome annotation databases

Ensembl

ENSRNOG00000011507. Rattus norvegicus. [Contig view]

GeneID

84591.

KEGG

rno:84591.

Organism-specific databases

RGD

69437. Pick1.

Phylogenomic databases

HOVERGEN

Q9EP80.

Gene expression databases

ArrayExpress

Q9EP80.

GermOnline

ENSRNOG00000011507. Rattus norvegicus.

Family and domain databases

InterPro

IPR010504. Arfaptin.
IPR001478. PDZ/DHR/GLGF.
[Graphical view]

Gene3D

G3DSA:1.20.1270.60. Arfaptin. 1 hit.

Pfam

PF06456. Arfaptin. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]

SMART

SM00228. PDZ. 1 hit.
[Graphical view]

PROSITE

PS50870. AH. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

617193.

Entry information

Entry name

PICK1_RAT

Accession

Primary (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:	June 16, 2009
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)