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Protein

Phospholipase A-2-activating protein

Gene

PLAA

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

Functioni

Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (PubMed:27753622). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (By similarity). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (PubMed:27753622). Plays a role in cerebellar Purkinje cell development (By similarity). 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:18291623, PubMed:28007986).By similarity3 Publications

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processNeurogenesis

Enzyme and pathway databases

SignaLinkiQ9Y263

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipase A-2-activating protein
Short name:
PLA2P
Short name:
PLAP
Gene namesi
Name:PLAA
Synonyms:PLAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000137055.14
HGNCiHGNC:9043 PLAA
MIMi603873 gene
neXtProtiNX_Q9Y263

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

Involvement in diseasei

Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy.
See also OMIM:617527
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07927623G → V in NDMSBA. 1 PublicationCorresponds to variant dbSNP:rs747956857Ensembl.1
Natural variantiVAR_079277752L → F in NDMSBA; no effect on protein stability; no effect on subcellular localization; decreased function in positive regulation of cytosolic phospholipase A2 activity; in patient cells homozygous for the mutation. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi9373
MIMi617527 phenotype
OpenTargetsiENSG00000137055
PharmGKBiPA33370

Chemistry databases

ChEMBLiCHEMBL6114

Polymorphism and mutation databases

BioMutaiPLAA
DMDMi108935868

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000511301 – 795Phospholipase A-2-activating proteinAdd BLAST795

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50PhosphoserineCombined sources1
Modified residuei529N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y263
MaxQBiQ9Y263
PaxDbiQ9Y263
PeptideAtlasiQ9Y263
PRIDEiQ9Y263

PTM databases

iPTMnetiQ9Y263
PhosphoSitePlusiQ9Y263

Expressioni

Inductioni

Up-regulated by tumor necrosis factor alpha (TNF-alpha) (at protein level) (PubMed:18291623).1 Publication

Gene expression databases

BgeeiENSG00000137055
CleanExiHS_PLAA
ExpressionAtlasiQ9Y263 baseline and differential
GenevisibleiQ9Y263 HS

Organism-specific databases

HPAiCAB005035
HPA020994
HPA020996

Interactioni

Subunit structurei

Interacts with ubiquitin (PubMed:19423704). Interacts with UBXN6, VCP and YOD1; may form a complex involved in macroautophagy (PubMed:27753622, PubMed:19887378).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114774, 42 interactors
IntActiQ9Y263, 16 interactors
MINTiQ9Y263
STRINGi9606.ENSP00000380460

Chemistry databases

BindingDBiQ9Y263

Structurei

Secondary structure

1795
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi390 – 392Combined sources3
Beta strandi394 – 396Combined sources3
Beta strandi399 – 407Combined sources9
Beta strandi410 – 412Combined sources3
Beta strandi416 – 420Combined sources5
Helixi426 – 437Combined sources12
Helixi443 – 455Combined sources13
Turni457 – 460Combined sources4
Helixi548 – 559Combined sources12
Helixi564 – 566Combined sources3
Helixi571 – 584Combined sources14
Helixi593 – 603Combined sources11
Turni607 – 609Combined sources3
Helixi611 – 620Combined sources10
Helixi624 – 631Combined sources8
Turni633 – 635Combined sources3
Helixi636 – 645Combined sources10
Helixi653 – 665Combined sources13
Helixi666 – 668Combined sources3
Helixi670 – 678Combined sources9
Helixi680 – 688Combined sources9
Helixi689 – 691Combined sources3
Helixi696 – 715Combined sources20
Helixi719 – 733Combined sources15
Helixi739 – 753Combined sources15
Helixi757 – 765Combined sources9
Helixi768 – 771Combined sources4
Helixi772 – 777Combined sources6
Helixi782 – 792Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K89NMR-A386-465[»]
2K8ANMR-A386-465[»]
2K8BNMR-B386-465[»]
2K8CNMR-B386-465[»]
3EBBX-ray1.90A/B/C/D511-795[»]
ProteinModelPortaliQ9Y263
SMRiQ9Y263
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y263

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 – 794PULPROSITE-ProRule annotationAdd BLAST262
Repeati546 – 588ARM 1Add BLAST43
Repeati589 – 620ARM 2Add BLAST32
Repeati621 – 669ARM 3Add BLAST49
Repeati670 – 715ARM 4Add BLAST46
Repeati716 – 755ARM 5Add BLAST40
Repeati756 – 795ARM 6Add BLAST40

Domaini

The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus.1 Publication
The PFU domain mediates interaction with ubiquitin.1 Publication

Sequence similaritiesi

Belongs to the WD repeat PLAP family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0301 Eukaryota
ENOG410XS67 LUCA
GeneTreeiENSGT00550000074944
HOGENOMiHOG000174247
HOVERGENiHBG008204
InParanoidiQ9Y263
KOiK14018
OMAiKEGQVQM
OrthoDBiEOG091G06FX
PhylomeDBiQ9Y263
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
IPR016024 ARM-type_fold
IPR015155 PFU
IPR038122 PFU_sf
IPR033510 PLAA/Doa1/Lub1
IPR013535 PUL_dom
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR19849 PTHR19849, 2 hits
PfamiView protein in Pfam
PF09070 PFU, 1 hit
PF08324 PUL, 1 hit
PF00400 WD40, 6 hits
SMARTiView protein in SMART
SM00320 WD40, 7 hits
SUPFAMiSSF48371 SSF48371, 1 hit
SSF50978 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.

Q9Y263-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTSGATRYRL SCSLRGHELD VRGLVCCAYP PGAFVSVSRD RTTRLWAPDS
60 70 80 90 100
PNRSFTEMHC MSGHSNFVSC VCIIPSSDIY PHGLIATGGN DHNICIFSLD
110 120 130 140 150
SPMPLYILKG HKNTVCSLSS GKFGTLLSGS WDTTAKVWLN DKCMMTLQGH
160 170 180 190 200
TAAVWAVKIL PEQGLMLTGS ADKTVKLWKA GRCERTFSGH EDCVRGLAIL
210 220 230 240 250
SETEFLSCAN DASIRRWQIT GECLEVYYGH TNYIYSISVF PNCRDFVTTA
260 270 280 290 300
EDRSLRIWKH GECAQTIRLP AQSIWCCCVL DNGDIVVGAS DGIIRVFTES
310 320 330 340 350
EDRTASAEEI KAFEKELSHA TIDSKTGDLG DINAEQLPGR EHLNEPGTRE
360 370 380 390 400
GQTRLIRDGE KVEAYQWSVS EGRWIKIGDV VGSSGANQQT SGKVLYEGKE
410 420 430 440 450
FDYVFSIDVN EGGPSYKLPY NTSDDPWLTA YNFLQKNDLN PMFLDQVAKF
460 470 480 490 500
IIDNTKGQML GLGNPSFSDP FTGGGRYVPG SSGSSNTLPT ADPFTGAGRY
510 520 530 540 550
VPGSASMGTT MAGVDPFTGN SAYRSAASKT MNIYFPKKEA VTFDQANPTQ
560 570 580 590 600
ILGKLKELNG TAPEEKKLTE DDLILLEKIL SLICNSSSEK PTVQQLQILW
610 620 630 640 650
KAINCPEDIV FPALDILRLS IKHPSVNENF CNEKEGAQFS SHLINLLNPK
660 670 680 690 700
GKPANQLLAL RTFCNCFVGQ AGQKLMMSQR ESLMSHAIEL KSGSNKNIHI
710 720 730 740 750
ALATLALNYS VCFHKDHNIE GKAQCLSLIS TILEVVQDLE ATFRLLVALG
760 770 780 790
TLISDDSNAV QLAKSLGVDS QIKKYSSVSE PAKVSECCRF ILNLL
Length:795
Mass (Da):87,157
Last modified:June 13, 2006 - v2
Checksum:iD6E7330AC9891637
GO

Sequence cautioni

The sequence AAD03030 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAD42075 differs from that shown. Reason: Frameshift at position 698.Curated
The sequence AAD42075 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA92105 differs from that shown. Reason: Erroneous termination at position 545. Translated as Gln.Curated
The sequence BAD97264 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB42881 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAH72641 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14L → F in AAD42075 (PubMed:10644453).Curated1
Sequence conflicti57E → D in AAD42075 (PubMed:10644453).Curated1
Sequence conflicti86A → F in AAD42075 (PubMed:10644453).Curated1
Sequence conflicti97F → L in AAD42075 (PubMed:10644453).Curated1
Sequence conflicti172D → G in BAA91803 (PubMed:14702039).Curated1
Sequence conflicti363E → K in BAD97264 (Ref. 6) Curated1
Sequence conflicti422T → A in AAD42075 (PubMed:10644453).Curated1
Sequence conflicti520N → S in BAA92105 (PubMed:14702039).Curated1
Sequence conflicti531M → L in AAD42075 (PubMed:10644453).Curated1
Sequence conflicti541V → L in AAD42075 (PubMed:10644453).Curated1
Sequence conflicti746L → P in AAD42075 (PubMed:10644453).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07927623G → V in NDMSBA. 1 PublicationCorresponds to variant dbSNP:rs747956857Ensembl.1
Natural variantiVAR_079277752L → F in NDMSBA; no effect on protein stability; no effect on subcellular localization; decreased function in positive regulation of cytosolic phospholipase A2 activity; in patient cells homozygous for the mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK001642 mRNA Translation: BAA91803.1
AK002143 mRNA Translation: BAA92105.1 Sequence problems.
AL133608 mRNA Translation: CAB63739.1
AL356133 Genomic DNA Translation: CAH72641.1 Sequence problems.
BC032551 mRNA Translation: AAH32551.1
AF145020 mRNA Translation: AAD42075.1 Sequence problems.
AK223544 mRNA Translation: BAD97264.1 Different initiation.
AJ238243 mRNA Translation: CAB42881.1 Different initiation.
AF083395 mRNA Translation: AAD03030.1 Different initiation.
CCDSiCCDS35000.1
PIRiT43447
RefSeqiNP_001026859.1, NM_001031689.2
UniGeneiHs.27182

Genome annotation databases

EnsembliENST00000397292; ENSP00000380460; ENSG00000137055
GeneIDi9373
KEGGihsa:9373
UCSCiuc003zqd.4 human

Similar proteinsi

Entry informationi

Entry nameiPLAP_HUMAN
AccessioniPrimary (citable) accession number: Q9Y263
Secondary accession number(s): Q53EU5
, Q5VY33, Q9NUL8, Q9NVE9, Q9UF53, Q9Y5L1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: June 13, 2006
Last modified: April 25, 2018
This is version 165 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
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Main funding by: National Institutes of Health