PICK1_MOUSE
ID PICK1_MOUSE Reviewed; 416 AA.
AC Q62083; E9PY04;
DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=PRKCA-binding protein;
DE AltName: Full=Protein interacting with C kinase 1;
DE AltName: Full=Protein kinase C-alpha-binding protein;
GN Name=Pick1; Synonyms=Prkcabp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PRKCA, AND PHOSPHORYLATION.
RC TISSUE=T-cell;
RX PubMed=7844141; DOI=10.1083/jcb.128.3.263;
RA Staudinger J., Zhou J., Burgess R., Elledge S.J., Olson E.N.;
RT "PICK1: a perinuclear binding protein and substrate for protein kinase C
RT isolated by the yeast two-hybrid system.";
RL J. Cell Biol. 128:263-271(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP HOMODIMERIZATION, AND MUTAGENESIS OF LYS-27 AND 27-LYS-ASP-28.
RX PubMed=9405395; DOI=10.1074/jbc.272.51.32019;
RA Staudinger J., Lu J., Olson E.N.;
RT "Specific interaction of the PDZ domain protein PICK1 with the COOH
RT terminus of protein kinase C-alpha.";
RL J. Biol. Chem. 272:32019-32024(1997).
RN [4]
RP INTERACTION WITH EPHA7; EPHB1 AND EPHB2, AND PHOSPHORYLATION.
RX PubMed=9883737; DOI=10.1016/s0896-6273(00)80663-7;
RA Torres R., Firestein B.L., Dong H., Staudinger J., Olson E.N.,
RA Huganir R.L., Bredt D.S., Gale N.W., Yancopoulos G.D.;
RT "PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors
RT and their ephrin ligands.";
RL Neuron 21:1453-1463(1998).
RN [5]
RP INTERACTION WITH GRIA2 ISOFORM 1.
RX PubMed=10340301; DOI=10.1016/s0028-3908(98)00230-5;
RA Dev K.K., Nishimune A., Henley J.M., Nakanishi S.;
RT "The protein kinase C alpha binding protein PICK1 interacts with short but
RT not long form alternative splice variants of AMPA receptor subunits.";
RL Neuropharmacology 38:635-644(1999).
RN [6]
RP INTERACTION WITH ERBB2.
RX PubMed=11278603; DOI=10.1074/jbc.m010032200;
RA Jaulin-Bastard F., Saito H., Le Bivic A., Ollendorff V., Marchetto S.,
RA Birnbaum D., Borg J.-P.;
RT "The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-
RT 95/DLG/ZO-1 domain proteins.";
RL J. Biol. Chem. 276:15256-15263(2001).
RN [7]
RP INTERACTION WITH GRM7.
RX PubMed=12065412; DOI=10.1093/emboj/cdf313;
RA Perroy J., El Far O., Bertaso F., Pin J.P., Betz H., Bockaert J., Fagni L.;
RT "PICK1 is required for the control of synaptic transmission by the
RT metabotropic glutamate receptor 7.";
RL EMBO J. 21:2990-2999(2002).
RN [8]
RP MUTAGENESIS OF LYS-27 AND 27-LYS-ASP-28, AND FUNCTION.
RX PubMed=14976185; DOI=10.1074/jbc.m313078200;
RA Deval E., Salinas M., Baron A., Lingueglia E., Lazdunski M.;
RT "ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion
RT channel subunit in sensory neurons via the partner protein PICK-1.";
RL J. Biol. Chem. 279:19531-19539(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION.
RX PubMed=20445062; DOI=10.1523/jneurosci.6276-09.2010;
RA Clem R.L., Anggono V., Huganir R.L.;
RT "PICK1 regulates incorporation of calcium-permeable AMPA receptors during
RT cortical synaptic strengthening.";
RL J. Neurosci. 30:6360-6366(2010).
RN [11]
RP PALMITOYLATION AT CYS-414, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-414.
RX PubMed=24068808; DOI=10.1523/jneurosci.1283-13.2013;
RA Thomas G.M., Hayashi T., Huganir R.L., Linden D.J.;
RT "DHHC8-dependent PICK1 palmitoylation is required for induction of
RT cerebellar long-term synaptic depression.";
RL J. Neurosci. 33:15401-15407(2013).
CC -!- FUNCTION: Probable adapter protein that bind to and organize the
CC subcellular localization of a variety of membrane proteins containing
CC some PDZ recognition sequence. Involved in the clustering of various
CC receptors, possibly by acting at the receptor internalization level.
CC Plays a role in synaptic plasticity by regulating the trafficking and
CC internalization of AMPA receptors. May be regulated upon PRKCA
CC activation. May regulate ASIC1/ASIC3 channel. Regulates actin
CC polymerization by inhibiting the actin-nucleating activity of the
CC Arp2/3 complex; the function is competitive with nucleation promoting
CC factors and is linked to neuronal morphology regulation and AMPA
CC receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex
CC involved in regulation of synaptic plasicity of excitatory synapses and
CC required for spine shrinkage during long-term depression (LTD).
CC Involved in regulation of astrocyte morphology, antagonistic to Arp2/3
CC complex activator WASL/N-WASP function. {ECO:0000269|PubMed:14976185,
CC ECO:0000269|PubMed:20445062}.
CC -!- SUBUNIT: Monomer and homodimer. Interacts with CXADR. Interacts
CC presynaptically with the glutamate receptors GRIA2, GRIA3, GRIK3,
CC isoform 3 of GRIA4, isoform A of GRM4, GRM7 and GRM8; with NAPA and
CC NAPB; and with BTG2. The interaction with NAPA and NAPB disrupts the
CC interaction with GRIA2, conducting to the internalization of GRIA2.
CC Interacts with PRKCA; with the amine transporters SLC6A2 and SLC6A3;
CC with the channels ASIC1 and ASIC2; with the GTP-binding proteins ARF1
CC and ARF3; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and
CC EPHB2; with ERBB2 and through its PDZ domain with the C-terminal tail
CC of PRLHR. Interacts with UNC5A. Interacts (via AH domain) with
CC NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and
CC associates with the ARP2/3 complex. Interacts (via PDZ domain) with
CC ARF1 (activated); the interaction blocks Arp2/3 complex inhibition.
CC {ECO:0000269|PubMed:10340301, ECO:0000269|PubMed:11278603,
CC ECO:0000269|PubMed:12065412, ECO:0000269|PubMed:7844141,
CC ECO:0000269|PubMed:9883737}.
CC -!- INTERACTION:
CC Q62083; P97411: Ica1; NbExp=2; IntAct=EBI-77550, EBI-16056188;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Membrane {ECO:0000269|PubMed:24068808}; Lipid-anchor
CC {ECO:0000269|PubMed:24068808}. Postsynaptic density {ECO:0000250}.
CC Synapse, synaptosome {ECO:0000250}. Cytoplasm, cytoskeleton
CC {ECO:0000250}. Note=Also membrane-associated, present at excitatory
CC synapses. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined, with highest
CC levels in brain and testes and lowest levels in lung.
CC -!- DOMAIN: The AH domain mediates binding to F-actin. {ECO:0000250}.
CC -!- DOMAIN: The unoccupied PDZ domain is probably involved in allosteric
CC modulation by forming an intramolecular bridge with the AH domain
CC leading to a 'closed' formation. Binding of a PDZ ligand, such as
CC GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex
CC thus enhanced inhibition of actin polymerization (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-82 appears to inhibit the interaction with
CC AMPA receptors (By similarity). Phosphorylated on tyrosine residues by
CC EPHB2 and on serine or threonine residues by PKC. {ECO:0000250,
CC ECO:0000269|PubMed:7844141, ECO:0000269|PubMed:9883737}.
CC -!- PTM: Palmitoylation on Cys-414 is essential for long-term synaptic
CC depression (LTD). {ECO:0000269|PubMed:24068808}.
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DR EMBL; Z46720; CAA86675.1; -; mRNA.
DR EMBL; AL591913; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591921; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS27635.1; -.
DR PIR; A56486; A56486.
DR AlphaFoldDB; Q62083; -.
DR SMR; Q62083; -.
DR DIP; DIP-283N; -.
DR IntAct; Q62083; 7.
DR MINT; Q62083; -.
DR STRING; 10090.ENSMUSP00000128126; -.
DR iPTMnet; Q62083; -.
DR PhosphoSitePlus; Q62083; -.
DR SwissPalm; Q62083; -.
DR MaxQB; Q62083; -.
DR PaxDb; Q62083; -.
DR PRIDE; Q62083; -.
DR ProteomicsDB; 289420; -.
DR ABCD; Q62083; 1 sequenced antibody.
DR MGI; MGI:894645; Pick1.
DR eggNOG; KOG3651; Eukaryota.
DR InParanoid; Q62083; -.
DR Reactome; R-MMU-416993; Trafficking of GluR2-containing AMPA receptors.
DR ChiTaRS; Pick1; mouse.
DR PRO; PR:Q62083; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62083; protein.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0098842; C:postsynaptic early endosome; ISO:MGI.
DR GO; GO:0098843; C:postsynaptic endocytic zone; ISO:MGI.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0032588; C:trans-Golgi network membrane; IBA:GO_Central.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0071933; F:Arp2/3 complex binding; ISS:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:0140090; F:membrane curvature sensor activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; IMP:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0005484; F:SNAP receptor activity; ISO:MGI.
DR GO; GO:0036294; P:cellular response to decreased oxygen levels; ISS:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0097062; P:dendritic spine maintenance; ISS:UniProtKB.
DR GO; GO:0097061; P:dendritic spine organization; ISS:UniProtKB.
DR GO; GO:0021782; P:glial cell development; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0060292; P:long-term synaptic depression; ISS:UniProtKB.
DR GO; GO:0015844; P:monoamine transport; ISS:UniProtKB.
DR GO; GO:0034316; P:negative regulation of Arp2/3 complex-mediated actin nucleation; ISS:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISS:UniProtKB.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006605; P:protein targeting; IDA:MGI.
DR GO; GO:0043113; P:receptor clustering; IDA:UniProtKB.
DR GO; GO:0034315; P:regulation of Arp2/3 complex-mediated actin nucleation; IBA:GO_Central.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:MGI.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; ISO:MGI.
DR GO; GO:0050803; P:regulation of synapse structure or activity; NAS:UniProtKB.
DR CDD; cd07659; BAR_PICK1; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR010504; AH_dom.
DR InterPro; IPR030798; Arfaptin_fam.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR037959; PICK1_BAR.
DR PANTHER; PTHR12141; PTHR12141; 1.
DR Pfam; PF06456; Arfaptin; 1.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM01015; Arfaptin; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50870; AH; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Calcium; Cytoplasm; Cytoskeleton; Lipoprotein; Membrane;
KW Metal-binding; Palmitate; Phosphoprotein; Reference proteome; Synapse;
KW Synaptosome; Zinc.
FT CHAIN 1..416
FT /note="PRKCA-binding protein"
FT /id="PRO_0000058428"
FT DOMAIN 22..105
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 144..357
FT /note="AH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00294"
FT REGION 373..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 82
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRD5"
FT LIPID 414
FT /note="S-palmitoyl cysteine; by DHHC8"
FT /evidence="ECO:0000269|PubMed:24068808"
FT MUTAGEN 27..28
FT /note="KD->AA: Abolishes interaction with other proteins,
FT but not with itself. Partial loss of the ASIC1/ASIC3
FT channel regulation by PKC."
FT /evidence="ECO:0000269|PubMed:14976185,
FT ECO:0000269|PubMed:9405395"
FT MUTAGEN 27
FT /note="K->A: Does not abolish the interaction with PKCA."
FT /evidence="ECO:0000269|PubMed:14976185,
FT ECO:0000269|PubMed:9405395"
FT MUTAGEN 414
FT /note="C->S: Fails to rescue cerebellar LTD in PICK1
FT knockouts."
FT /evidence="ECO:0000269|PubMed:24068808"
FT CONFLICT 179..180
FT /note="EL -> DV (in Ref. 1; CAA86675)"
FT /evidence="ECO:0000305"
FT CONFLICT 198..199
FT /note="EP -> DA (in Ref. 1; CAA86675)"
FT /evidence="ECO:0000305"
FT CONFLICT 279..280
FT /note="GP -> AA (in Ref. 1; CAA86675)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 416 AA; 46597 MW; 437369D0AB7DCE7B CRC64;
MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV QVFDNTPAAL
DGTVAAGDEI TGVNGKSIKG KTKVEVAKMI QEVKGEVTIH YNKLQADPKQ GMSLDIVLKK
VKHRLVENMS SGTADALGLS RAILCNDGLV KRLEELERTA ELYKGMTEHT KNLLRAFYEL
SQTHRAFGDV FSVIGVREPQ PAASEAFVKF ADAHRSIEKF GIRLLKTIKP MLTDLNTYLN
KAIPDTRLTI KKYLDVKFEY LSYCLKVKEM DDEEYSCIGP RRALYRVSTG NYEYRLILRC
RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRFVST MSKYYNDCYA VLQDADVFPI
EVDLAHTTLA YGPNQGSFTD GEEEDEEEED GAAREVSKDA CGATGPTDKG GSWCDS
