Q62083 (PICK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
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. 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.8 Ref.9
Subunit structure	Monomer and homodimer. Interacts with PRKCA; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; the channel protein ACCN1; and with ERBB2. Interacts presynaptically with the glutamate receptors GRIA3, the isoform 1 of GRIA2, the isoform A of GRM4, GRM7 and GRM8; with NAPA and NAPB. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with the monoamine transporters SLC6A2 and SLC6A3; with the channel protein ACCN2; with the GTP-binding proteins ARF1 and ARF3; and EPHB2; and with ERBB2. Interacts with UNC5A, CXADR and through its PDZ domain with the C-terminal tail of PRLHR By similarity. Interacts (via AH domain) with NCS1/FREQ in a calcium-dependent manner By similarity. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Cytoplasm › perinuclear region. Cell junction › synapse. Note: Also present at excitatory synapses.
Tissue specificity	Expressed in all tissues examined, with highest levels in brain and testes and lowest levels in lung.
Post-translational modification	Phosphorylated on tyrosine residues by EPHB2 and on serine or threonine residues by PKC. Ref.1 Ref.4 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 component	Cell junction Cytoplasm Synapse
Ligand	Calcium Metal-binding Zinc
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
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 intracellular protein kinase cascade Non-traceable author statement Ref.1. Source: UniProtKB monoamine transport Inferred from sequence or structural similarity. Source: UniProtKB multicellular organismal development Non-traceable author statement Ref.4. Source: UniProtKB protein homooligomerization Traceable author statement Ref.3. Source: UniProtKB protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein targeting Inferred from direct assay. Source: MGI receptor clustering Inferred from direct assay Ref.4. Source: UniProtKB regulation of synapse structure and activity Non-traceable author statement Ref.4. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay Ref.1. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW mitochondrion Inferred from direct assay. Source: MGI perinuclear region of cytoplasm Inferred from direct assay Ref.1. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB presynaptic membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATPase activity Inferred from direct assay. 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 kinase C binding Inferred from physical interaction Ref.1. Source: UniProtKB receptor binding Inferred from physical interaction Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 416	416	PRKCA-binding protein		PRO_0000058428
Regions
	Domain	22 – 105	84	PDZ
	Domain	144 – 357	214	AH
	Compositional bias	382 – 389	8	Poly-Glu
Sites
	Metal binding	44	1	Zinc By similarity
	Metal binding	46	1	Zinc By similarity
Amino acid modifications
	Modified residue	18	1	Phosphothreonine By similarity
	Modified residue	82	1	Phosphothreonine By similarity
Experimental info
	Mutagenesis	27 – 28	2	KD → AA: Abolishes interaction with other proteins, but not with itself. Partial loss of the ACCN3/ACCN2 channel regulation by PKC. Ref.3 Ref.8
	Mutagenesis	27	1	K → A: Does not abolish the interaction with PKCA. Ref.3 Ref.8
	Sequence conflict	179 – 180	2	EL → DV in CAA86675. Ref.1
	Sequence conflict	198 – 199	2	EP → DA in CAA86675. Ref.1
	Sequence conflict	279 – 280	2	GP → AA in CAA86675. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q62083 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 437369D0AB7DCE7B	FASTA	416	46,597
	10 20 30 40 50 60 MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV QVFDNTPAAL 70 80 90 100 110 120 DGTVAAGDEI TGVNGKSIKG 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 DDEEYSCIGP RRALYRVSTG NYEYRLILRC 310 320 330 340 350 360 RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRFVST MSKYYNDCYA VLQDADVFPI 370 380 390 400 410 EVDLAHTTLA YGPNQGSFTD GEEEDEEEED GAAREVSKDA CGATGPTDKG GSWCDS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 7844141] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PRKCA, PHOSPHORYLATION. Tissue: T-cell.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[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: 9405395] [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: 9883737] [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: 10340301] [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: 11278603] [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: 12065412] [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: 14976185] [Abstract] Cited for: MUTAGENESIS OF LYS-27 AND 27-LYS-ASP-28, FUNCTION.
[9]	"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: 20445062] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z46720 mRNA. Translation: CAA86675.1. AL591913 Genomic DNA. No translation available. AL591921 Genomic DNA. No translation available.
IPI	IPI00310563.
PIR	A56486.
UniGene	Mm.259464.
3D structure databases
ProteinModelPortal	Q62083.
SMR	Q62083. Positions 14-110, 145-355.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-283N.
IntAct	Q62083. 4 interactions.
MINT	MINT-223505.
STRING	Q62083.
PTM databases
PhosphoSite	Q62083.
Proteomic databases
PRIDE	Q62083.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000166882; ENSMUSP00000132770; ENSMUSG00000068206.
Organism-specific databases
MGI	MGI:894645. Pick1.
Phylogenomic databases
eggNOG	roNOG06087.
HOVERGEN	HBG053600.
Gene expression databases
ArrayExpress	Q62083.
Bgee	Q62083.
CleanEx	MM_PICK1.
Genevestigator	Q62083.
GermOnline	ENSMUSG00000068206. Mus musculus.
Family and domain databases
InterPro	IPR010504. Arfaptin_homology_dom. 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	SM01015. Arfaptin. 1 hit. SM00228. PDZ. 1 hit. [Graphical view]
SUPFAM	SSF50156. PDZ. 1 hit.
PROSITE	PS50870. AH. 1 hit. PS50106. PDZ. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

PICK1_MOUSE

Accession

Primary (citable) accession number: Q62083
Secondary accession number(s): E9PY04

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 2, 2002
Last sequence update:	July 27, 2011
Last modified:	January 25, 2012
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program