PLA2G4A phospholipase A2 group IVA [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLA2G4Aprovided by HGNC
Official Full Name: phospholipase A2 group IVAprovided by HGNC
Primary source: HGNC:HGNC:9035
See related: Ensembl:ENSG00000116711 MIM:600522; AllianceGenome:HGNC:9035
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GURDP; cPLA2; PLA2G4; cPLA2-alpha
Summary: This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca(2+) levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]
Expression: Ubiquitous expression in urinary bladder (RPKM 6.0), adrenal (RPKM 5.6) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q31.1

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (186828949..186988981)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (186183301..186343553)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (186798081..186958113)

Chromosome 1 - NC_000001.11 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
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?

PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.
Title: PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer.
The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis.
Title: The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis.
Association between PLA2G4A and P2RX7 genes and eosinophilic phenotype and environment with pediatric asthma.
Title: Association between PLA2G4A and P2RX7 genes and eosinophilic phenotype and environment with pediatric asthma.
Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.
Title: Calcium-dependent cytosolic phospholipase A(2) activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.
Genetic polymorphism data support a relationship between schizophrenia and microsatellite variability in PLA2G4A in Northern Europeans not Han Chinese.
Title: Genetic polymorphism data support a relationship between schizophrenia and microsatellite variability in PLA2G4A in Northern Europeans not Han Chinese.
Omega-3 versus Omega-6 fatty acid availability is controlled by hydrophobic site geometries of phospholipase A2s.
Title: Omega-3 versus Omega-6 fatty acid availability is controlled by hydrophobic site geometries of phospholipase A(2)s.
A synergy between mechanosensitive calcium- and membrane-binding mediates tension-sensing by C2-like domains.
Title: A synergy between mechanosensitive calcium- and membrane-binding mediates tension-sensing by C2-like domains.
PLA2G4A promotes right-sided colorectal cancer progression by inducing CD39+gammadelta Treg polarization.
Title: PLA2G4A promotes right-sided colorectal cancer progression by inducing CD39+γδ Treg polarization.
Inhibition of Cytosolic Phospholipase A2alpha Induces Apoptosis in Multiple Myeloma Cells.
Title: Inhibition of Cytosolic Phospholipase A2α Induces Apoptosis in Multiple Myeloma Cells.
Protein dynamics analysis identifies candidate cancer driver genes and mutations in TCGA data.
Title: Protein dynamics analysis identifies candidate cancer driver genes and mutations in TCGA data.

Submit: New GeneRIF Correction See all GeneRIFs (161)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder MedGen: C5567651 OMIM: 618372 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32 EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 causes an activation of phospholipase A2, resulting in the increased release of arachidonic acid, which may sensitize the NMDA receptor	PubMed
	env	HIV-1 gp120 induces a specific phospholipase A2 (PLA2) activation in lymphocytes through binding to CD4, but this effect is not sufficient to accomplish virus/cell fusion	PubMed
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of phospholipase A2, group IVA (PLA2G4A) in primary human brain microvascular endothelial cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G67877 (e-PCR)
- UniSTS:225589

AL034257 (e-PCR)
- UniSTS:94079

D1S3460 (e-PCR), detects polymorphism
- UniSTS:33961

GDB:321239 (e-PCR)
- UniSTS:156588

GDB:582583 (e-PCR)
- UniSTS:157881

RH17731 (e-PCR)
- UniSTS:38860

PLA2G4A (e-PCR)
- UniSTS:503764

SHGC-35515 (e-PCR)
- UniSTS:57313

D13AT1 (e-PCR)
- UniSTS:239336

RH104487 (e-PCR)
- UniSTS:98799

D1S3128 (e-PCR)
- UniSTS:18428

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables O-acyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent phospholipase A2 activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-dependent phospholipase A2 activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent phospholipase A2 activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables calcium-dependent phospholipid binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-dependent phospholipid binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium-independent phospholipase A2 activity	IDA Inferred from Direct Assay more info	PubMed
enables ceramide 1-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables lysophospholipase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-4-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-5-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phospholipase A2 activity	IDA Inferred from Direct Assay more info	PubMed
enables phospholipase A2 activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in arachidonate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in arachidonate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in arachidonate secretion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to antibiotic	IEA Inferred from Electronic Annotation more info
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
involved_in glycerol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in glycerophospholipid catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in icosanoid metabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in leukotriene biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoacylglycerol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylcholine acyl-chain remodeling	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylcholine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylglycerol catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in platelet activating factor biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of T-helper 1 type immune response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of macrophage activation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of platelet activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of prostaglandin secretion	IEA Inferred from Electronic Annotation more info
involved_in prostaglandin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in prostaglandin biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in prostaglandin biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in mitochondrial inner membrane	TAS Traceable Author Statement more info
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: cytosolic phospholipase A2

Names: calcium-dependent phospholipid-binding protein; lysophospholipase; phosphatidylcholine 2-acylhydrolase; phospholipase A2, group IVA (cytosolic, calcium-dependent)

NP_001298122.2

EC 3.1.1.4

EC 3.1.1.5

NP_077734.2

EC 3.1.1.4

EC 3.1.1.5

XP_005245324.2

EC 3.1.1.4

EC 3.1.1.5

XP_011507944.1

EC 3.1.1.4

EC 3.1.1.5

XP_047278555.1

EC 3.1.1.4

EC 3.1.1.5

XP_054193055.1

EC 3.1.1.4

EC 3.1.1.5

XP_054193056.1

EC 3.1.1.4

EC 3.1.1.5

XP_054193057.1

EC 3.1.1.4

EC 3.1.1.5

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.

Genomic

NG_012203.2 RefSeqGene

Range

5050..165082

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_596

mRNA and Protein(s)

NM_001311193.2 → NP_001298122.2 cytosolic phospholipase A2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two in-frame exons in the central coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.

Source sequence(s)

AL022147, AL049797

UniProtKB/TrEMBL

B4DZI4

Conserved Domains (2) summary

cd07200
Location:114 → 670

cPLA2_Grp-IVA; Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent

cd04036
Location:20 → 129

C2_cPLA2; C2 domain present in cytosolic PhosphoLipase A2 (cPLA2)
NM_024420.3 → NP_077734.2 cytosolic phospholipase A2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL049797, BC114340, BX118890, DA451491, M72393

Consensus CDS

CCDS1372.1

UniProtKB/Swiss-Prot

B1AKG4, P47712, Q29R80

UniProtKB/TrEMBL

A8K2S1

Related

ENSP00000356436.3, ENST00000367466.4

Conserved Domains (2) summary

cd07200
Location:144 → 730

cPLA2_Grp-IVA; Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent

cd04036
Location:20 → 138

C2_cPLA2; C2 domain present in cytosolic PhosphoLipase A2 (cPLA2)

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_000001.11 Reference GRCh38.p14 Primary Assembly

Range

186828949..186988981

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011509642.3 → XP_011507944.1 cytosolic phospholipase A2 isoform X2

See identical proteins and their annotated locations for XP_011507944.1

UniProtKB/Swiss-Prot

B1AKG4, P47712, Q29R80

UniProtKB/TrEMBL

A8K2S1

Conserved Domains (2) summary

cd07200
Location:144 → 730

cPLA2_Grp-IVA; Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent

cd04036
Location:20 → 138

C2_cPLA2; C2 domain present in cytosolic PhosphoLipase A2 (cPLA2)
XM_047422599.1 → XP_047278555.1 cytosolic phospholipase A2 isoform X3
XM_005245267.5 → XP_005245324.2 cytosolic phospholipase A2 isoform X1

UniProtKB/TrEMBL

A8K2S1

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

186183301..186343553

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054337081.1 → XP_054193056.1 cytosolic phospholipase A2 isoform X2

UniProtKB/TrEMBL

A8K2S1
XM_054337082.1 → XP_054193057.1 cytosolic phospholipase A2 isoform X3
XM_054337080.1 → XP_054193055.1 cytosolic phospholipase A2 isoform X1

UniProtKB/TrEMBL

A8K2S1