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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]
PLA2G4A (Phospholipase A2 Group IVA) is a Protein Coding gene. Diseases associated with PLA2G4A include Gastrointestinal Ulceration, Recurrent, With Dysfunctional Platelets and Cryptogenic Multifocal Ulcerous Stenosing Enteritis. Among its related pathways are DAG and IP3 signaling and Sweet Taste Signaling. Gene Ontology (GO) annotations related to this gene include calcium ion binding and phospholipase A2 activity. An important paralog of this gene is PLA2G4E.
Phospholipases are a group of enzymes that hydrolyze phospholipids into fatty acids and other lipophilic molecules. There are four major classes; phospholipase A, phospholipase B, phosphoinositide-specific phospholipase C and phospholipase D.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH01J186828 | Promoter/Enhancer | 2 | EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas | 604.8 | +0.9 | 916 | 3.1 | PRDM10 ZNF512 ZNF692 PRDM1 ZSCAN4 POLR2A RUNX3 CEBPB ZNF316 ZSCAN5C | PLA2G4A TPR PTGS2 piR-56133-014 | |
GH01J186849 | Enhancer | 0.7 | FANTOM5 | 17.5 | +20.6 | 20553 | 0.3 | RELA REST IKZF2 EED CEBPB SP1 RELB RUNX3 ATF3 NR3C1 | PLA2G4A PTGS2 piR-56133-014 | |
GH01J186848 | Enhancer | 0.6 | FANTOM5 | 17.7 | +20.0 | 20039 | 0.2 | ZNF692 ZSCAN4 ZNF248 ATF3 SIX5 FOXP1 ZNF112 FOS ZNF114 ZBTB33 | ENSG00000228238 PLA2G4A PDC-AS1 ODR4 PTGS2 piR-56133-014 | |
GH01J186738 | Enhancer | 0.8 | FANTOM5 Ensembl | 10.8 | -90.0 | -90029 | 1.4 | CEBPB ARID3A RUNX3 JUNB BATF MTA2 SPI1 EZH2 CREM | PTGS2 PLA2G4A PACERR ODR4 HSALNG0009106 RF00994-073 | |
GH01J186882 | Enhancer | 0.5 | Ensembl | 11.6 | +53.7 | 53652 | 0.8 | ATF7 ATF2 JUND NR3C1 JUN | PLA2G4A piR-56133-014 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004620 | phospholipase activity | IEA | -- |
GO:0004622 | lysophospholipase activity | IEA,IDA | 12672805 |
GO:0004623 | phospholipase A2 activity | IBA,NAS | 8381049 |
GO:0005509 | calcium ion binding | IBA,IDA | 9430701 |
GO:0005544 | calcium-dependent phospholipid binding | IBA,IDA | 9665851 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000139 | Golgi membrane | IDA | 11375391 |
GO:0005634 | nucleus | IBA | 21873635 |
GO:0005635 | nuclear envelope | IDA | 11375391 |
GO:0005737 | cytoplasm | IBA,IDA | 11375391 |
GO:0005743 | mitochondrial inner membrane | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Glycerophospholipid biosynthesis | ||
2 | Acyl chain remodelling of PE |
.30
|
|
3 | DAG and IP3 signaling |
Neurophysiological process PGE2-induced pain processing
.38
|
|
4 | Immune response Fc epsilon RI pathway |
Immune response Fc epsilon RI pathway
.44
|
|
5 | Linoleic acid metabolism |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001516 | prostaglandin biosynthetic process | IEA,IMP | 18451993 |
GO:0002827 | positive regulation of T-helper 1 type immune response | IEA | -- |
GO:0006071 | glycerol metabolic process | IEA | -- |
GO:0006629 | lipid metabolic process | IEA | -- |
GO:0006640 | monoacylglycerol biosynthetic process | IDA | 7794891 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Fluticasone propionate | Approved | Pharma | Target, inhibitor, antagonist | Selective high affinity glucocorticoid receptor agonist | 0 | |
Carbenicillin | Approved, Investigational | Pharma | Enzyme, inhibitor | 1 | ||
Epirubicin | Approved | Pharma | Enzyme, inhibitor | 483 | ||
Orlistat | Approved, Investigational | Pharma | Enzyme, inhibitor | Lipase inhibitor for obesity treatment, Pancreatic, gastric and carboxylester lipase inhibitor; antiobesity and antihypercholesterolemic activity | 61 | |
Urethane | Approved, Withdrawn | Pharma | Enzyme, substrate | 14 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
Arachidic acid |
|
506-30-9 |
|
|||
Glycerylphosphorylethanolamine |
|
1190-00-7 |
|
|||
Heptadecanoic acid |
|
506-12-7 |
|
|||
Heptadecanoyl CoA |
|
3546-17-6 |
|
|||
LysoPC(0:0/18:0) |
|
4421-58-3 |
|
Compound | Action | Cas Number |
---|---|---|
AACOCF3 | Phospholipase A2 inhibitor | 149301-79-1 |
Edelfosine | Selective PI-PLC inhibitor, also PAF receptor agonist | 77286-66-9 |
m-3M3FBS | Phospholipase C activator | 200933-14-8 |
o-3M3FBS | Inactive analog of m-3M3FBS (Cat. No. 1941) | 313981-55-4 |
U 73122 | Phospholipase C inhibitor | 112648-68-7 |
Compound | Action | Cas Number |
---|---|---|
AACOCF3 | Inhibitor of cPLA2/anandamide hydrolysis/FAAH | 149301-79-1 |
Clofazimine | Tuberculosis drug | 2030-63-9 |
CP-91149 | Selective inhibitor of glycogen phosphorylase | 186392-40-5 |
PACOCF3 | CPLA2 and iPLA2 inhibitor | 141022-99-3 |
Varespladib (LY315920) | HnsPLA inhibitor,potent and selective | 172732-68-2 |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | PLA2G4A 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | PLA2G4A 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | PLA2G4A 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PLA2G4A 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | PLA2G4A 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Pla2g4a 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Pla2g4a 30 17 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | PLA2G4A 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | PLA2G4A 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | pla2g4a 30 |
|
||
Str.20412 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | pla2g4a-prov 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | pla2g4a 31 |
|
OneToMany | |
cpla2 30 31 |
|
OneToMany | |||
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.2704 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.6135 31 |
|
OneToOne | |
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.2601 30 |
|
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
721606 | Benign: not provided | 186,965,587(+) | G/A | SYNONYMOUS_VARIANT | |
725133 | Likely Benign: not provided | 186,979,349(+) | C/T | SYNONYMOUS_VARIANT | |
734303 | Benign: not provided | 186,894,188(+) | G/A | MISSENSE_VARIANT | |
738215 | Benign: not provided | 186,932,874(+) | G/A | MISSENSE_VARIANT | |
741451 | Likely Benign: not provided | 186,893,141(+) | T/C | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv1010484 | CNV | insertion | 20482838 |
esv1093925 | CNV | insertion | 17803354 |
esv2720350 | CNV | deletion | 23290073 |
esv2762854 | CNV | gain | 21179565 |
esv3339194 | CNV | insertion | 20981092 |
esv3543755 | CNV | deletion | 23714750 |
nsv1079016 | OTHER | inversion | 25765185 |
nsv3877 | CNV | insertion | 18451855 |
nsv466272 | CNV | loss | 19166990 |
nsv548406 | CNV | loss | 21841781 |
nsv548407 | CNV | loss | 21841781 |
Disorder | Aliases | PubMed IDs |
---|---|---|
gastrointestinal ulceration, recurrent, with dysfunctional platelets |
|
|
cryptogenic multifocal ulcerous stenosing enteritis |
|
|
penis squamous cell carcinoma |
|
|
krabbe disease |
|
|
hypereosinophilic syndrome |
|