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Protein

Phospholipase A-2-activating protein

Gene

Plaa

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (By similarity). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (PubMed:28413018). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (By similarity). Plays a role in cerebellar Purkinje cell development (PubMed:28413018). Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis (PubMed:28007986).By similarity2 Publications

GO - Molecular functioni

  • phospholipase A2 activator activity Source: MGI
  • ubiquitin binding Source: GO_Central

GO - Biological processi

  • cellular response to lipopolysaccharide Source: UniProtKB
  • inflammatory response Source: MGI
  • macroautophagy Source: UniProtKB
  • negative regulation of protein K63-linked ubiquitination Source: UniProtKB
  • positive regulation of dendrite extension Source: UniProtKB
  • positive regulation of neuron migration Source: UniProtKB
  • positive regulation of phospholipase A2 activity Source: UniProtKB
  • positive regulation of synaptic vesicle recycling Source: UniProtKB
  • prostaglandin metabolic process Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: UniProtKB
  • ubiquitin recycling Source: GO_Central

Keywordsi

Molecular functionDevelopmental protein
Biological processNeurogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipase A-2-activating protein
Short name:
PLA2P
Short name:
PLAP
Gene namesi
Name:Plaa
Synonyms:Plap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:104810 Plaa

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, Cytoplasm, Nucleus, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice die perinatally and exhibit spleen, lung and brain developmental anomalies (PubMed:28413018, PubMed:28007986). Display less matured and differentiated embryonic cortical neurons (PubMed:28007986). Display reduced ubiquitin-dependent membrane protein trafficking from early to late endosomes (PubMed:28413018). Show reduced prostaglandin E2 biosynthesis in embryonic brain, lung and heart, but not in liver at 18 dpc (PubMed:28007986).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23G → V: Loss of protein abundance. Increased abundance of ubiquitinated synaptic proteins. Decreased ubiquitin-mediated trafficking of membrane proteins through the endolysosomal pathway. Decreased synaptic vesicle recycling. Decreased cerebellar Purkinje cell migration and dendrite extension. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000511311 – 794Phospholipase A-2-activating proteinAdd BLAST794

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50PhosphoserineBy similarity1
Modified residuei529N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP27612
MaxQBiP27612
PaxDbiP27612
PeptideAtlasiP27612
PRIDEiP27612

PTM databases

iPTMnetiP27612
PhosphoSitePlusiP27612

Expressioni

Tissue specificityi

Expressed in the brain, with highest levels in hippocampal neurons, cerebellar granular cell layer and Purkinje cells (PubMed:28413018).1 Publication

Developmental stagei

At stage 11.5 dpc ubiquitously expressed (PubMed:28413018).1 Publication

Inductioni

In smooth muscle and endothelial cells by leukotriene D4, by tumor necrosis factor in endothelial cells and by uric acid crystals in macrophages.1 Publication

Gene expression databases

BgeeiENSMUSG00000028577
CleanExiMM_PLAA
ExpressionAtlasiP27612 baseline and differential
GenevisibleiP27612 MM

Interactioni

Subunit structurei

Interacts with ubiquitin. Interacts with UBXN6, VCP and YOD1; may form a complex involved in macroautophagy.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202224, 5 interactors
IntActiP27612, 1 interactor
MINTiP27612
STRINGi10090.ENSMUSP00000102724

Structurei

3D structure databases

ProteinModelPortaliP27612
SMRiP27612
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati17 – 56WD 1Add BLAST40
Repeati63 – 107WD 2Add BLAST45
Repeati110 – 148WD 3Add BLAST39
Repeati149 – 188WD 4Add BLAST40
Repeati190 – 227WD 5Add BLAST38
Repeati229 – 268WD 6Add BLAST40
Repeati270 – 307WD 7Add BLAST38
Domaini366 – 465PFUPROSITE-ProRule annotationAdd BLAST100
Domaini533 – 793PULPROSITE-ProRule annotationAdd BLAST261
Repeati546 – 588ARM 1Add BLAST43
Repeati589 – 620ARM 2Add BLAST32
Repeati621 – 668ARM 3Add BLAST48
Repeati669 – 714ARM 4Add BLAST46
Repeati715 – 754ARM 5Add BLAST40
Repeati755 – 794ARM 6Add BLAST40

Domaini

The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus.By similarity
The PFU domain mediates interaction with ubiquitin.By similarity

Sequence similaritiesi

Belongs to the WD repeat PLAP family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0301 Eukaryota
ENOG410XS67 LUCA
GeneTreeiENSGT00550000074944
HOGENOMiHOG000174247
HOVERGENiHBG008204
InParanoidiP27612
KOiK14018
OMAiKEGQVQM
OrthoDBiEOG091G06FX
TreeFamiTF105944

Family and domain databases

Gene3Di1.10.150.410, 1 hit
1.25.10.10, 1 hit
2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR015155 PFU
IPR038122 PFU_sf
IPR013535 PUL_dom
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF09070 PFU, 1 hit
PF08324 PUL, 1 hit
PF00400 WD40, 6 hits
SMARTiView protein in SMART
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS51394 PFU, 1 hit
PS51396 PUL, 1 hit
PS50082 WD_REPEATS_2, 3 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequencei

Sequence statusi: Complete.

P27612-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASGASRYRL SCSLPGHELD VRGLVCCLYP PGAFVSVSRD RTTRLWAPDS
60 70 80 90 100
PNRGFTEMHC MSGHSNFVSC VCIIPSSDIY PHGLIATGGN DHNICIFSLD
110 120 130 140 150
SPMPLYILKG HKDTVCSLSS GKFGTLLSGS WDTTAKVWLN DKCMMTLQGH
160 170 180 190 200
TAAVWAVKIL PEQGLMLTGS ADKTIKLWKA GRCERTFLGH EDCVRGLAIL
210 220 230 240 250
SETEFLSCAN DASIRRWQIT GECLEVYFGH TNYIYSISVF PNSKDFVTTA
260 270 280 290 300
EDRSLRIWKH GECAQTIRLP AQSIWCCCVL ENGDIVVGAS DGIIRVFTES
310 320 330 340 350
EERTASAEEI KAFERELSQA TIDSKTGDLG DINAEQLPGR EHLSEPGTRE
360 370 380 390 400
GQTRLIRDGE RVEAYQWSVS DGRWIKIGDV VGSSGANQQT SGKVLYEGKE
410 420 430 440 450
FDYVFSIDVN EGGPSYKLPY NVSDDPWLVA YNFLQKNDLN PMFLDQVAKF
460 470 480 490 500
IIDNTKGQTL GLGNTSFSDP FTGGGRYVPG TSGPSNTVQT ADPFTGAGRY
510 520 530 540 550
MPGSAGMDTT MTGVDPFTGN SAYRSAASKT VNIYFPKKEA LTFDQANPTQ
560 570 580 590 600
ILGKLKELNG TAPEEKKLTE DDLVLLEKIL SLICNNSSEK PTAQQLQILW
610 620 630 640 650
KAINWPEDIV FPALDILRLS IKHPNVNENF CNEKGDQFSS HLINLLNPKG
660 670 680 690 700
KPANQLLALR TFCNCFVSQA GQKLMMSQRE SLMSHAIELK SGSNKNIHIA
710 720 730 740 750
LATLTLNYSV CFHKDHNIEG KAQCLSVIST ILEVVQDLEA TFRLLVALGT
760 770 780 790
LISDDSNAIQ LAKSLGVDSQ IKKYVSVSEP AKVSECCRLV LHLL
Length:794
Mass (Da):87,221
Last modified:July 27, 2011 - v4
Checksum:i7D8B1D55B07563CC
GO

Sequence cautioni

The sequence AAA39943 differs from that shown. Several frameshifts and contaminating sequence.Curated
The sequence described in Ref. 3 differs from that shown. Reason: Frameshift at position 697.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60C → Y in AAA39943 (PubMed:19468303).Curated1
Sequence conflicti70C → Y in AAA39943 (PubMed:19468303).Curated1
Sequence conflicti300 – 301SE → AD (PubMed:7665086).Curated2
Sequence conflicti528S → T in BAC36064 (PubMed:16141072).Curated1
Sequence conflicti546A → T (PubMed:7665086).Curated1
Sequence conflicti593A → R (PubMed:7665086).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK075934 mRNA Translation: BAC36064.1
AL732597 Genomic DNA Translation: CAM19635.1
CH466527 Genomic DNA Translation: EDL30936.1
BC139355 mRNA Translation: AAI39356.1
BC139356 mRNA Translation: AAI39357.1
BC139773 mRNA Translation: AAI39774.1
M57958 mRNA Translation: AAA39943.1 Sequence problems.
CCDSiCCDS18359.1
PIRiA40963
RefSeqiNP_766283.2, NM_172695.2
UniGeneiMm.490101
Mm.491195

Genome annotation databases

EnsembliENSMUST00000107107; ENSMUSP00000102724; ENSMUSG00000028577
GeneIDi18786
KEGGimmu:18786
UCSCiuc008tsd.1 mouse

Similar proteinsi

Entry informationi

Entry nameiPLAP_MOUSE
AccessioniPrimary (citable) accession number: P27612
Secondary accession number(s): A4QPD6, Q8C6C4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 163 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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