P97570 · PLPL9_RAT

  • Protein
    85/88 kDa calcium-independent phospholipase A2
  • Gene
    Pla2g6
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 and A2 activity respectively), producing lysophospholipids that are used in deacylation-reacylation cycles (PubMed:18937505, PubMed:9111008).
Hydrolyzes both saturated and unsaturated long fatty acyl chains in various glycerophospholipid classes such as phosphatidylcholines, phosphatidylethanolamines and phosphatidates, with a preference for hydrolysis at sn-2 position. Can further hydrolyze lysophospholipids carrying saturated fatty acyl chains (lysophospholipase activity) (PubMed:18937505).
Upon oxidative stress, contributes to remodeling of mitochondrial phospholipids in pancreatic beta cells, in a repair mechanism to reduce oxidized lipid content (PubMed:24648512).
Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains from cardiolipins, yielding monolysocardiolipins that can be reacylated with unoxidized fatty acyls to regenerate native cardiolipin species. Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic islets, releasing oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates (HETEs) (PubMed:24648512).
Has thioesterase activity toward fatty-acyl CoA releasing CoA-SH known to facilitate fatty acid transport and beta-oxidation in mitochondria particularly in skeletal muscle (PubMed:18937505).
Plays a role in regulation of membrane dynamics and homeostasis. Selectively hydrolyzes sn-2 arachidonoyl group in plasmalogen phospholipids, structural components of lipid rafts and myelin (By similarity).
Regulates F-actin polymerization at the pseudopods, which is required for both speed and directionality of MCP1/CCL2-induced monocyte chemotaxis (By similarity).
Targets membrane phospholipids to produce potent lipid signaling messengers. Generates lysophosphatidate (LPA, 1-acyl-glycerol-3-phosphate), which acts via G-protein receptors in various cell types. Has phospholipase A2 activity toward platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), likely playing a role in inactivation of this potent pro-inflammatory signaling lipid (By similarity).
In response to glucose, amplifies calcium influx in pancreatic beta cells to promote INS secretion (By similarity).

Catalytic activity

  • a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H+
    This reaction proceeds in the forward direction.
    EC:3.1.1.4 (UniProtKB | ENZYME | Rhea)
  • 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+ + hexadecanoate
    This reaction proceeds in the forward direction.
  • 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+
    This reaction proceeds in the forward direction.
  • 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+
    This reaction proceeds in the forward direction.
  • 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+
    This reaction proceeds in the forward direction.
  • 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-octadecanoyl-sn-glycero-3-phosphocholine + H+
    This reaction proceeds in the forward direction.
  • 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + H+
    This reaction proceeds in the forward direction.
  • 1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1-hexadecanoyl-sn-glycero-3-phosphate + H+ + hexadecanoate
    This reaction proceeds in the forward direction.
  • a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid + H+ + sn-glycerol 3-phosphocholine
    This reaction proceeds in the forward direction.
    EC:3.1.1.5 (UniProtKB | ENZYME | Rhea)
  • 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H+ + hexadecanoate + sn-glycerol 3-phosphocholine
    This reaction proceeds in the forward direction.
  • 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + sn-glycerol 3-phosphocholine
    This reaction proceeds in the forward direction.
  • 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + sn-glycerol 3-phosphocholine
    This reaction proceeds in the forward direction.
  • 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-O-hexadecyl-sn-glycero-3-phosphocholine + H+
    This reaction proceeds in the forward direction.
  • 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H+
    This reaction proceeds in the forward direction.
  • H2O + hexadecanoyl-CoA = CoA + H+ + hexadecanoate
    This reaction proceeds in the forward direction.
    EC:3.1.2.2 (UniProtKB | ENZYME | Rhea)
  • 1',3'-bis[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = (9Z)-octadecenoate + 1'-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3'-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H+
    This reaction proceeds in the forward direction.
  • 1'-[1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho]-3'-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H2O = (9Z)-octadecenoate + 1',3'-bis-[1-(9Z-octadecenoyl)-sn-glycero-3-phospho]-glycerol + H+
    This reaction proceeds in the forward direction.
  • 1',3'-bis-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + H2O = (9Z,12Z)-octadecadienoate + 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + H+
    This reaction proceeds in the backward direction.
  • 1-octadecanoyl-2-(15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoethanolamine + 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + H+
    This reaction proceeds in the forward direction.

Activity regulation

Activated by ATP (PubMed:18937505, PubMed:9111008).
Inhibited by calcium-activated calmodulin (PubMed:11118454, PubMed:18937505).
Inhibited by bromoenol lactone (BEL) (PubMed:18937505).

pH Dependence

Optimum pH is 7.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site520Nucleophile
Active site653Proton acceptor

GO annotations

AspectTerm
Cellular Componentextracellular space
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrion
Cellular Componentplasma membrane
Cellular Componentpseudopodium
Molecular Function1-alkyl-2-acetylglycerophosphocholine esterase activity
Molecular FunctionATP-dependent protein binding
Molecular Functioncalcium-independent phospholipase A2 activity
Molecular Functioncalmodulin binding
Molecular Functionidentical protein binding
Molecular Functionlong-chain fatty acyl-CoA hydrolase activity
Molecular Functionlysophospholipase activity
Molecular Functionphospholipase A2 activity
Molecular Functionprotein kinase binding
Molecular Functionserine hydrolase activity
Biological Processantibacterial humoral response
Biological Processcardiolipin acyl-chain remodeling
Biological Processcardiolipin biosynthetic process
Biological Processchemotaxis
Biological Processmaternal process involved in female pregnancy
Biological Processmemory
Biological Processnegative regulation of synaptic transmission, glutamatergic
Biological Processphosphatidic acid metabolic process
Biological Processphosphatidylcholine catabolic process
Biological Processphosphatidylethanolamine catabolic process
Biological Processplatelet activating factor metabolic process
Biological Processpositive regulation of arachidonic acid secretion
Biological Processpositive regulation of ceramide biosynthetic process
Biological Processpositive regulation of cytosolic calcium ion concentration
Biological Processpositive regulation of exocytosis
Biological Processpositive regulation of insulin secretion involved in cellular response to glucose stimulus
Biological Processpositive regulation of protein kinase C signaling
Biological Processpositive regulation of protein phosphorylation
Biological Processpositive regulation of release of cytochrome c from mitochondria
Biological Processresponse to endoplasmic reticulum stress
Biological Processurinary bladder smooth muscle contraction
Biological Processvasodilation

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    85/88 kDa calcium-independent phospholipase A2
  • EC number
  • Short names
    CaI-PLA2
  • Alternative names
    • 2-lysophosphatidylcholine acylhydrolase (EC:3.1.1.5
      ) . EC:3.1.1.5 (UniProtKB | ENZYME | Rhea)
    • Group VI phospholipase A2 (GVI PLA2)
    • Intracellular membrane-associated calcium-independent phospholipase A2 beta (iPLA2-beta)
    • Palmitoyl-CoA hydrolase (EC:3.1.2.2
      ) . EC:3.1.2.2 (UniProtKB | ENZYME | Rhea)
    • Patatin-like phospholipase domain-containing protein 9 (PNPLA9)

Gene names

    • Name
      Pla2g6
    • Synonyms
      Pnpla9

Organism names

  • Taxonomic identifier
  • Strains
    • Sprague-Dawley
    • Brown Norway
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P97570
  • Secondary accessions
    • G3V7M8
    • Q66HD1

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Cell membrane
Mitochondrion
Note: Recruited to the membrane-enriched pseudopods upon MCP1/CCL2 stimulation in monocytes.

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane481-501Helical
Transmembrane512-532Helical

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000670391-80785/88 kDa calcium-independent phospholipase A2
Modified residue13Phosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in pancreatic beta-cells (PubMed:9111008).
Expressed in skeletal muscle (at protein level) (PubMed:18937505).

Gene expression databases

Interaction

Subunit

Homodimer formed by catalytic domains tightly interacting through a large hydrophobic interface. The contact area involves 3 alpha helices, several loops and a part of the beta sheet from each monomer. Both active sites of the dimer are in close proximity adopting an open conformation that provide sufficient space for phospholipid access and favoring cooperativity in deacylation-reacylation reactions. Each monomer has 9 ankyrin repeats stacked side-by-side in an elongated structure oriented outwards from the catalytic core.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for repeat, domain, motif, region.

TypeIDPosition(s)Description
Repeat120-147ANK 1
Repeat151-181ANK 1
Repeat185-215ANK 2
Repeat219-248ANK 3
Repeat251-281ANK 4
Repeat286-312ANK 5
Repeat316-345ANK 6
Repeat349-378ANK 7
Repeat382-403ANK 9
Domain482-666PNPLA
Motif486-491GXGXXG
Motif518-522GXSXG
Motif653-655DGA/G
Region678-687Calmodulin-binding (1-9-14 motif)
Region749-760Calmodulin-binding (IQ motif)

Domain

Has two putative calmodulin binding domains, the 1-9-14 and IQ motifs (PubMed:11118454).
One calmodulin molecule interacts with PLA2G6 dimer, likely through 1-9-14 motif on each monomer (By similarity).
Binds calmodulin in a calcium-dependent way (PubMed:11118454).

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

P97570-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    Long
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    807
  • Mass (Da)
    89,556
  • Last updated
    2012-10-31 v2
  • Checksum
    1B9018AE1B2D252F
MQFFGRLVNTLSSVTNLFSNPFRVKEVSLADYASSERVREEGQLILLQNASNRTWDCVLVSPRNPQSGFRLFQLESEADALVNFQQYSSQLPPFYESSVQVLHVEVLQHLTDLIRNHPSWTVTHLAVELGIRECFHHSRIISCANSTENEEGCTPLHLACRKGDSEILVELVQYCHAQMDVTDNKGETAFHYAVQGDNPQVLQLLGKNASAGLNQVNNQGLTPLHLACQMGKQEMVRVLLLCNARCNIMGPGGFPIHTAMKFSQKGCAEMIISMDSNQIHSKDPRYGASPLHWAKNAEMARMLLKRGCDVDSTSASGNTALHVAVTRNRFDCVMVLLTYGANAGARGEHGNTPLHLAMSKDNMEMVKALIVFGAEVDTPNDFGETPAFIASKISKLITRKALLTLLKTVGADYHFPFIQGVSTEQSSAAGPHPFFSLDRTQPPTISLNNLELQDLMPVSRARKPAFILSSMRDEKRSHDHLLCLDGGGVKGLVIIQLLIAIEKASGVATKDLFDWVAGTSTGGILALAILHSKSMAYMRGVYFRMKDEVFRGSRPYESGPLEEFLKREFGEHTKMTDVKKPKVMLTGTLSDRQPAELHLFRNYDAPEAVREPRCTPNINLKPPTQPADQLVWRAARSSGAAPTYFRPNGRFLDGGLLANNPTLDAMTEIHEYNQDMIRKGQGNKVKKLSIVVSLGTGKSPQVPVTCVDVFRPSNPWELAKTVFGAKELGKMVVDCCTDPDGRAVDRARAWCEMVGIQYFRLNPQLGSDIMLDEVSDAVLVNALWETEVYIYEHREEFQKLVQLLLSP

P97570-2

  • Name
    Short
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 396-451: LITRKALLTLLKTVGADYHFPFIQGVSTEQSSAAGPHPFFSLDRTQPPTISLNNLE → Q

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8L2Q8C9A0A8L2Q8C9_RATPla2g6770
A0A8L2Q8G5A0A8L2Q8G5_RATPla2g6844
A0A8L2R578A0A8L2R578_RATPla2g6760

Features

Showing features for sequence conflict, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict24in Ref. 1; AAC53136
Sequence conflict58in Ref. 1; AAC53136
Sequence conflict68in Ref. 1; AAC53136
Sequence conflict80in Ref. 1; AAC53136
Sequence conflict99in Ref. 1; AAC53136
Sequence conflict109in Ref. 1; AAC53136
Sequence conflict142in Ref. 1; AAC53136
Alternative sequenceVSP_044365396-451in isoform Short
Sequence conflict477in Ref. 1; AAC53136
Sequence conflict793in Ref. 1; AAC53136

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U51898
EMBL· GenBank· DDBJ
AAC53136.1
EMBL· GenBank· DDBJ
mRNA
AABR06052011
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH473950
EMBL· GenBank· DDBJ
EDM15808.1
EMBL· GenBank· DDBJ
Genomic DNA
CH473950
EMBL· GenBank· DDBJ
EDM15809.1
EMBL· GenBank· DDBJ
Genomic DNA
BC081916
EMBL· GenBank· DDBJ
AAH81916.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any 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. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp