PLAA phospholipase A2 activating protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLAAprovided by HGNC
Official Full Name: phospholipase A2 activating proteinprovided by HGNC
Primary source: HGNC:HGNC:9043
See related: Ensembl:ENSG00000137055 MIM:603873; AllianceGenome:HGNC:9043
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DOA1; PLAP; PLA2P; NDMSBA
Summary: Predicted to enable ubiquitin binding activity. Involved in cellular response to lipopolysaccharide; macroautophagy; and positive regulation of phospholipase A2 activity. Located in cytoplasm; extracellular exosome; and nucleus. [provided by Alliance of Genome Resources, Oct 2024]
Expression: Ubiquitous expression in testis (RPKM 6.9), bone marrow (RPKM 5.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p21.2

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (26903372..26947242, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (26913987..26957845, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (26903370..26947240, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PLAA suppresses ovarian cancer metastasis via METTL3-mediated m(6)A modification of TRPC3 mRNA.
Title: PLAA suppresses ovarian cancer metastasis via METTL3-mediated m(6)A modification of TRPC3 mRNA.
In both human and mouse, hypomorphic mutations in the ubiquitin adaptor protein PLAA cause an infantile-lethal neurodysfunction syndrome with seizures.
Title: PLAA Mutations Cause a Lethal Infantile Epileptic Encephalopathy by Disrupting Ubiquitin-Mediated Endolysosomal Degradation of Synaptic Proteins.
Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response.
Title: VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy.
This study presented that Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy.
Title: Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy.
This review provides evidence that 1,25-dihydroxy vitamin D3 stimulates PLA2 via PLAA and CaMKII, a process initiated by Pdia3/PLAA interaction, which further triggers CaMKII-dependent PLA2 activation. [review]
Title: Membrane-mediated actions of 1,25-dihydroxy vitamin D3: a review of the roles of phospholipase A2 activating protein and Ca(2+)/calmodulin-dependent protein kinase II.
Observational study of gene-disease association. (HuGE Navigator)
Title: Associations of 9p21 variants with cutaneous malignant melanoma, nevi, and pigmentation phenotypes in melanoma-prone families with and without CDKN2A mutations.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort.
Structural basis for ubiquitin recognition by a novel domain from the human phospholipase A2-activating protein
Title: Structural basis for ubiquitin recognition by a novel domain from human phospholipase A2-activating protein.
identified one stimulatory element, with Sp1 binding sites, and one inhibitory element, in exon 1 of the plaa gene
Title: Alteration in the activation state of new inflammation-associated targets by phospholipase A2-activating protein (PLAA).
Function assignment to conserved residues in mammalian alkaline phosphatases.
Title: Function assignment to conserved residues in mammalian alkaline phosphatases.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies MedGen: C4479631 OMIM: 617527 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW208417 (e-PCR)
- UniSTS:179030

D9S1696 (e-PCR)
- UniSTS:57949

MARC_66694-66695:1195518466:3 (e-PCR)
- UniSTS:508285

RH44824 (e-PCR)
- UniSTS:14776

D9S1061E (e-PCR)
- UniSTS:151278

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables phospholipase A2 activator activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cellular response to lipopolysaccharide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein K63-linked ubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
involved_in phospholipid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of dendrite extension	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuron migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of phospholipase A2 activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of synaptic vesicle recycling	ISS Inferred from Sequence or Structural Similarity more info
involved_in prostaglandin metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in ubiquitin recycling	IBA Inferred from Biological aspect of Ancestor more info
involved_in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: phospholipase A-2-activating protein

Names: DOA1 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001031689.3 → NP_001026859.1 phospholipase A-2-activating protein isoform 1

See identical proteins and their annotated locations for NP_001026859.1

Status: VALIDATED

Source sequence(s)

AL356133, BC032551, DA591576

Consensus CDS

CCDS35000.1

UniProtKB/Swiss-Prot

Q53EU5, Q5VY33, Q9NUL8, Q9NVE9, Q9UF53, Q9Y263, Q9Y5L1

Related

ENSP00000380460.3, ENST00000397292.8

Conserved Domains (6) summary

COG2319
Location:6 → 296

WD40; WD40 repeat [General function prediction only]

cd00200
Location:10 → 297

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

pfam05831
Location:298 → 352

GAGE; GAGE protein

pfam08324
Location:536 → 789

PUL; PUL domain

pfam09070
Location:346 → 458

PFU; PFU (PLAA family ubiquitin binding)

sd00039
Location:26 → 63

7WD40; WD40 repeat [structural motif]
NM_001321546.2 → NP_001308475.1 phospholipase A-2-activating protein isoform 2

Status: VALIDATED

Source sequence(s)

AL356133

Conserved Domains (6) summary

COG2319
Location:6 → 296

WD40; WD40 repeat [General function prediction only]

cd00200
Location:10 → 297

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

pfam05831
Location:298 → 352

GAGE; GAGE protein

pfam08324
Location:513 → 766

PUL; PUL domain

pfam09070
Location:346 → 458

PFU; PFU (PLAA family ubiquitin binding)

sd00039
Location:26 → 63

7WD40; WD40 repeat [structural motif]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

26903372..26947242 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047424083.1 → XP_047280039.1 phospholipase A-2-activating protein isoform X1

Related

ENSP00000429372.1, ENST00000520884.5
XM_011518072.4 → XP_011516374.1 phospholipase A-2-activating protein isoform X3

UniProtKB/TrEMBL

E5RIM3

Conserved Domains (5) summary

COG2319
Location:6 → 296

WD40; WD40 repeat [General function prediction only]

cd00200
Location:10 → 297

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

pfam05831
Location:298 → 352

GAGE; GAGE protein

pfam09070
Location:346 → 458

PFU; PFU (PLAA family ubiquitin binding)

sd00039
Location:69 → 110

7WD40; WD40 repeat [structural motif]
XM_017015319.3 → XP_016870808.1 phospholipase A-2-activating protein isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

26913987..26957845 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054364180.1 → XP_054220155.1 phospholipase A-2-activating protein isoform X1
XM_054364181.1 → XP_054220156.1 phospholipase A-2-activating protein isoform X2
XM_054364182.1 → XP_054220157.1 phospholipase A-2-activating protein isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_004253.3: Suppressed sequence

Description

NM_004253.3: This RefSeq was permanently suppressed because it contains a CDS that is incomplete at the 5' end.