PLA2G4A

Protein identityUniProt · HPA

UniProt accession

P47712

Gene

PLA2G4A

Ensembl

ENSG00000116711

Chromosome

1

Canonical length

749 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, RAS pathway related proteins

Subcellular location

Vesicles,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

749 residues, UniProt reviewed canonical sequence.

>P47712|PLA2G4A
     1  MSFIDPYQHI IVEHQYSHKF TVVVLRATKV TKGAFGDMLD TPDPYVELFI STTPDSRKRT
    61  RHFNNDINPV WNETFEFILD PNQENVLEIT LMDANYVMDE TLGTATFTVS SMKVGEKKEV
   121  PFIFNQVTEM VLEMSLEVCS CPDLRFSMAL CDQEKTFRQQ RKEHIRESMK KLLGPKNSEG
   181  LHSARDVPVV AILGSGGGFR AMVGFSGVMK ALYESGILDC ATYVAGLSGS TWYMSTLYSH
   241  PDFPEKGPEE INEELMKNVS HNPLLLLTPQ KVKRYVESLW KKKSSGQPVT FTDIFGMLIG
   301  ETLIHNRMNT TLSSLKEKVN TAQCPLPLFT CLHVKPDVSE LMFADWVEFS PYEIGMAKYG
   361  TFMAPDLFGS KFFMGTVVKK YEENPLHFLM GVWGSAFSIL FNRVLGVSGS QSRGSTMEEE
   421  LENITTKHIV SNDSSDSDDE SHEPKGTENE DAGSDYQSDN QASWIHRMIM ALVSDSALFN
   481  TREGRAGKVH NFMLGLNLNT SYPLSPLSDF ATQDSFDDDE LDAAVADPDE FERIYEPLDV
   541  KSKKIHVVDS GLTFNLPYPL ILRPQRGVDL IISFDFSARP SDSSPPFKEL LLAEKWAKMN
   601  KLPFPKIDPY VFDREGLKEC YVFKPKNPDM EKDCPTIIHF VLANINFRKY RAPGVPRETE
   661  EEKEIADFDI FDDPESPFST FNFQYPNQAF KRLHDLMHFN TLNNIDVIKE AMVESIEYRR
   721  QNPSRCSVSL SNVEARRFFN KEFLSKPKA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLA2G4A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

82 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PLA2G4A.

Disease | AllUniProt

Conditions PLA2G4A is implicated in, by any mechanism.

• Gastrointestinal ulceration, recurrent, with dysfunctional platelets (GURDP) MIM:618372

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 224 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.59

gnomAD pLI

0

gnomAD missense Z

2.35

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• arachidonate metabolic process
• arachidonate secretion
• cellular response to antibiotic
• establishment of localization in cell
• glycerol metabolic process
• glycerophospholipid catabolic process
• icosanoid metabolic process
• leukotriene biosynthetic process
• monoacylglycerol biosynthetic process
• phosphatidylcholine acyl-chain remodeling
• phosphatidylcholine catabolic process
• phosphatidylglycerol catabolic process
• platelet activating factor biosynthetic process
• positive regulation of macrophage activation
• positive regulation of platelet activation
• positive regulation of prostaglandin secretion
• positive regulation of T-helper 1 type immune response
• prostaglandin biosynthetic process
• regulation of cell population proliferation

Molecular functions

• calcium ion binding
• calcium-dependent phospholipase A2 activity
• calcium-dependent phospholipid binding
• calcium-independent phospholipase A2 activity
• ceramide 1-phosphate binding
• O-acyltransferase activity
• phosphatidylcholine lysophospholipase activity
• phosphatidylinositol-3-phosphate binding
• phosphatidylinositol-4-phosphate binding
• phosphatidylinositol-5-phosphate binding
• phospholipase A2 activity

Cellular components

• cytoplasm
• cytosol
• endoplasmic reticulum
• endoplasmic reticulum membrane
• Golgi apparatus
• Golgi membrane
• mitochondrial inner membrane
• nuclear envelope
• nucleus

Protein domainsUniProt · Pfam · InterPro

• C2 domain
• Lysophospholipase, catalytic domain
• Acyl transferase/acyl hydrolase/lysophospholipase
• C2 domain superfamily
• Cytosolic phospholipase A2, C2 domain
• C2 domain
• Lysophospholipase catalytic domain

KeywordsUniProt

• Calcium
• Cytoplasm
• Fatty acid biosynthesis
• Fatty acid metabolism
• Glycerol metabolism
• Golgi apparatus
• Hydrolase
• Isopeptide bond
• Leukotriene biosynthesis
• Lipid biosynthesis
• Lipid degradation
• Lipid metabolism
• Lipid-binding
• Membrane
• Metal-binding
• Nucleus
• Phospholipid degradation
• Phospholipid metabolism
• Phosphoprotein
• Prostaglandin biosynthesis
• Prostaglandin metabolism
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of PLA2G4A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• KAT5