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Protein

PRKCA-binding protein

Gene

PICK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competetive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi44ZincBy similarity1
Metal bindingi46ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActin-binding
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-202733. Cell surface interactions at the vascular wall.
R-HSA-416993. Trafficking of GluR2-containing AMPA receptors.
SignaLinkiQ9NRD5.
SIGNORiQ9NRD5.

Names & Taxonomyi

Protein namesi
Recommended name:
PRKCA-binding protein
Alternative name(s):
Protein interacting with C kinase 1
Protein kinase C-alpha-binding protein
Gene namesi
Name:PICK1
Synonyms:PRKCABP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100151.15.
HGNCiHGNC:9394. PICK1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Postsynaptic cell membrane, Synapse, Synaptosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27 – 28KD → AA: Abolishes interaction with other proteins, but not with itself. 3 Publications2
Mutagenesisi27K → E: Abolishes interaction with GRIA2, but not with PRKCA. 1 Publication1

Organism-specific databases

DisGeNETi9463.
MalaCardsiPICK1.
OpenTargetsiENSG00000100151.
PharmGKBiPA33760.

Polymorphism and mutation databases

BioMutaiPICK1.
DMDMi22095990.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000584271 – 415PRKCA-binding proteinAdd BLAST415

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei82Phosphothreonine1 Publication1
Lipidationi413S-palmitoyl cysteine; by DHHC8By similarity1

Post-translational modificationi

Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors.1 Publication
Palmitoylation on Cys-413 is essential for long-term synaptic depression (LTD).By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiQ9NRD5.
MaxQBiQ9NRD5.
PaxDbiQ9NRD5.
PeptideAtlasiQ9NRD5.
PRIDEiQ9NRD5.

PTM databases

iPTMnetiQ9NRD5.
PhosphoSitePlusiQ9NRD5.
SwissPalmiQ9NRD5.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000100151.
CleanExiHS_PICK1.
ExpressionAtlasiQ9NRD5. baseline and differential.
GenevisibleiQ9NRD5. HS.

Organism-specific databases

HPAiHPA067384.
HPA072674.

Interactioni

Subunit structurei

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 ASIC1 and ASIC2; 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. Interacts with UNC5A. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and associates with the ARP2/3 complex. Interacts (via PDZ domain) with ARF1 (activated); the interaction blocks Arp2/3 complex inhibition.6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114849. 70 interactors.
CORUMiQ9NRD5.
IntActiQ9NRD5. 343 interactors.
MINTiMINT-197903.
STRINGi9606.ENSP00000349465.

Structurei

Secondary structure

1415
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi21 – 26Combined sources6
Beta strandi34 – 39Combined sources6
Beta strandi47 – 52Combined sources6
Helixi57 – 61Combined sources5
Beta strandi69 – 73Combined sources5
Helixi83 – 92Combined sources10
Beta strandi95 – 102Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GZVX-ray1.12A19-105[»]
ProteinModelPortaliQ9NRD5.
SMRiQ9NRD5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NRD5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 105PDZPROSITE-ProRule annotationAdd BLAST84
Domaini144 – 357AHPROSITE-ProRule annotationAdd BLAST214

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi382 – 388Poly-Glu7

Domaini

The AH domain mediates binding to F-actin.By similarity
The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization (By similarity).By similarity

Phylogenomic databases

eggNOGiKOG3651. Eukaryota.
ENOG410YZG6. LUCA.
GeneTreeiENSGT00440000033690.
HOGENOMiHOG000007646.
HOVERGENiHBG053600.
InParanoidiQ9NRD5.
OMAiDAHRNIE.
OrthoDBiEOG091G08SM.
PhylomeDBiQ9NRD5.
TreeFamiTF314945.

Family and domain databases

Gene3Di1.20.1270.60. 1 hit.
InterProiView protein in InterPro
IPR027267. AH/BAR_dom_sf.
IPR010504. AH_dom.
IPR030798. Arfaptin_fam.
IPR001478. PDZ.
IPR036034. PDZ_sf.
PANTHERiPTHR12141. PTHR12141. 1 hit.
PfamiView protein in Pfam
PF06456. Arfaptin. 1 hit.
PF00595. PDZ. 1 hit.
SMARTiView protein in SMART
SM01015. Arfaptin. 1 hit.
SM00228. PDZ. 1 hit.
SUPFAMiSSF103657. SSF103657. 1 hit.
SSF50156. SSF50156. 1 hit.
PROSITEiView protein in PROSITE
PS50870. AH. 1 hit.
PS50106. PDZ. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRD5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MFADLDYDIE EDKLGIPTVP GKVTLQKDAQ NLIGISIGGG AQYCPCLYIV
60 70 80 90 100
QVFDNTPAAL DGTVAAGDEI TGVNGRSIKG KTKVEVAKMI QEVKGEVTIH
110 120 130 140 150
YNKLQADPKQ GMSLDIVLKK VKHRLVENMS SGTADALGLS RAILCNDGLV
160 170 180 190 200
KRLEELERTA ELYKGMTEHT KNLLRAFYEL SQTHRAFGDV FSVIGVREPQ
210 220 230 240 250
PAASEAFVKF ADAHRSIEKF GIRLLKTIKP MLTDLNTYLN KAIPDTRLTI
260 270 280 290 300
KKYLDVKFEY LSYCLKVKEM DDEEYSCIAL GEPLYRVSTG NYEYRLILRC
310 320 330 340 350
RQEARARFSQ MRKDVLEKME LLDQKHVQDI VFQLQRLVST MSKYYNDCYA
360 370 380 390 400
VLRDADVFPI EVDLAHTTLA YGLNQEEFTD GEEEEEEEDT AAGEPSRDTR
410
GAAGPLDKGG SWCDS
Length:415
Mass (Da):46,600
Last modified:August 2, 2002 - v2
Checksum:iC569FD8AA5028B90
GO
Isoform 2 (identifier: Q9NRD5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     279-364: ALGEPLYRVS...ADVFPIEVDL → VSVGGGGGLV...LHSYEALLSV
     365-415: Missing.

Note: No experimental confirmation available.
Show »
Length:364
Mass (Da):39,808
Checksum:i16BDC48FE02023BD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7Y → F in AAF97502 (Ref. 2) Curated1
Sequence conflicti16Missing in AAF97502 (Ref. 2) Curated1
Sequence conflicti236N → NI in AAF97502 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054902279 – 364ALGEP…IEVDL → VSVGGGGGLVLPPTWSARDS RWLRPTRERPGGLGWTLVPG DLGPSSQSRSLGLGVLGTRP GTTPSVWGTLGGKSDFLHSY EALLSV in isoform 2. 1 PublicationAdd BLAST86
Alternative sequenceiVSP_054903365 – 415Missing in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB026491 mRNA. Translation: BAA89294.1.
AF231710 mRNA. Translation: AAF97502.1.
AL049654 mRNA. Translation: CAB41082.1.
CR456550 mRNA. Translation: CAG30436.1.
AK092818 mRNA. Translation: BAG52614.1.
AL031587 Genomic DNA. Translation: CAB37478.1.
CH471095 Genomic DNA. Translation: EAW60208.1.
BC017561 mRNA. Translation: AAH17561.1.
CCDSiCCDS13965.1. [Q9NRD5-1]
PIRiJC7167.
RefSeqiNP_001034672.1. NM_001039583.1. [Q9NRD5-1]
NP_001034673.1. NM_001039584.1. [Q9NRD5-1]
NP_036539.1. NM_012407.3. [Q9NRD5-1]
UniGeneiHs.180871.

Genome annotation databases

EnsembliENST00000356976; ENSP00000349465; ENSG00000100151. [Q9NRD5-1]
ENST00000404072; ENSP00000385205; ENSG00000100151. [Q9NRD5-1]
GeneIDi9463.
KEGGihsa:9463.
UCSCiuc003auq.4. human. [Q9NRD5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPICK1_HUMAN
AccessioniPrimary (citable) accession number: Q9NRD5
Secondary accession number(s): B3KS52, O95906
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 2, 2002
Last sequence update: August 2, 2002
Last modified: November 22, 2017
This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references