PICK1_MACFA
ID PICK1_MACFA Reviewed; 415 AA.
AC Q4R7Q5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 82.
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; ORFNames=QtsA-14644;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Postsynaptic
CC density {ECO:0000250}. Synapse, synaptosome {ECO:0000250}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Note=Also membrane-associated, present at
CC excitatory synapses. {ECO:0000250}.
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. {ECO:0000250}.
CC -!- PTM: Palmitoylation on Cys-413 is essential for long-term synaptic
CC depression (LTD). {ECO:0000250}.
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DR EMBL; AB168760; BAE00867.1; -; mRNA.
DR AlphaFoldDB; Q4R7Q5; -.
DR SMR; Q4R7Q5; -.
DR STRING; 9541.XP_005567381.1; -.
DR eggNOG; KOG3651; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IEA:UniProt.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0071933; F:Arp2/3 complex binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; IEA:InterPro.
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:0060292; P:long-term synaptic depression; ISS:UniProtKB.
DR GO; GO:0034316; P:negative regulation of Arp2/3 complex-mediated actin nucleation; ISS:UniProtKB.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISS: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 2: Evidence at transcript level;
KW Actin-binding; Calcium; Cytoplasm; Cytoskeleton; Lipoprotein; Membrane;
KW Metal-binding; Palmitate; Phosphoprotein; Reference proteome; Synapse;
KW Synaptosome; Zinc.
FT CHAIN 1..415
FT /note="PRKCA-binding protein"
FT /id="PRO_0000318899"
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 376..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 377..392
FT /note="Acidic residues"
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 413
FT /note="S-palmitoyl cysteine; by DHHC8"
FT /evidence="ECO:0000250"
SQ SEQUENCE 415 AA; 46628 MW; 91FBB4A013D9E622 CRC64;
MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV QVFDNTPAAL
DGTVAAGDEI TGVNGRSIKG KTKVEVAKMI QEVKGEVTIH YNKLQADPKQ GMSLDIVLKK
VKHRLVENMS SGTADALGLS RAILCNDGLV KRLEELERTA ELYKGMTEHT KNLLRVFYEL
SQTHRAFGDV FSVIGVREPQ PAASEAFVKF ADAHRSIEKF GIRLLKTIKP MLTDLNTYLN
KAIPDTRLTI KKYLDVKFEY LSYCLKVKEM DDEEYSCIAL GEPLYRVSTG NYEYRLILRC
RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRLVST MSKYYNDCYA VLRDADVFPI
EVDLAHTTLA YGLNQEEFTD GEEEEEEEDT AAGEPSRDTR GAAGPLDKGG SWCDS
