P97570 · PLPL9_RAT
- Protein85/88 kDa calcium-independent phospholipase A2
- GenePla2g6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids807 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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.
- 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+ + hexadecanoateThis 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+ + hexadecanoateThis reaction proceeds in the forward direction.
- 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H+ + hexadecanoate + sn-glycerol 3-phosphocholineThis 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-phosphocholineThis 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-phosphocholineThis 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.
- 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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 520 | Nucleophile | ||||
Sequence: S | ||||||
Active site | 653 | Proton acceptor | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name85/88 kDa calcium-independent phospholipase A2
- EC number
- Short namesCaI-PLA2
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP97570
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Recruited to the membrane-enriched pseudopods upon MCP1/CCL2 stimulation in monocytes.
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 481-501 | Helical | ||||
Sequence: LLCLDGGGVKGLVIIQLLIAI | ||||||
Transmembrane | 512-532 | Helical | ||||
Sequence: LFDWVAGTSTGGILALAILHS |
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000067039 | 1-807 | 85/88 kDa calcium-independent phospholipase A2 | |||
Sequence: MQFFGRLVNTLSSVTNLFSNPFRVKEVSLADYASSERVREEGQLILLQNASNRTWDCVLVSPRNPQSGFRLFQLESEADALVNFQQYSSQLPPFYESSVQVLHVEVLQHLTDLIRNHPSWTVTHLAVELGIRECFHHSRIISCANSTENEEGCTPLHLACRKGDSEILVELVQYCHAQMDVTDNKGETAFHYAVQGDNPQVLQLLGKNASAGLNQVNNQGLTPLHLACQMGKQEMVRVLLLCNARCNIMGPGGFPIHTAMKFSQKGCAEMIISMDSNQIHSKDPRYGASPLHWAKNAEMARMLLKRGCDVDSTSASGNTALHVAVTRNRFDCVMVLLTYGANAGARGEHGNTPLHLAMSKDNMEMVKALIVFGAEVDTPNDFGETPAFIASKISKLITRKALLTLLKTVGADYHFPFIQGVSTEQSSAAGPHPFFSLDRTQPPTISLNNLELQDLMPVSRARKPAFILSSMRDEKRSHDHLLCLDGGGVKGLVIIQLLIAIEKASGVATKDLFDWVAGTSTGGILALAILHSKSMAYMRGVYFRMKDEVFRGSRPYESGPLEEFLKREFGEHTKMTDVKKPKVMLTGTLSDRQPAELHLFRNYDAPEAVREPRCTPNINLKPPTQPADQLVWRAARSSGAAPTYFRPNGRFLDGGLLANNPTLDAMTEIHEYNQDMIRKGQGNKVKKLSIVVSLGTGKSPQVPVTCVDVFRPSNPWELAKTVFGAKELGKMVVDCCTDPDGRAVDRARAWCEMVGIQYFRLNPQLGSDIMLDEVSDAVLVNALWETEVYIYEHREEFQKLVQLLLSP | ||||||
Modified residue | 13 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM 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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 120-147 | ANK 1 | ||||
Sequence: WTVTHLAVELGIRECFHHSRIISCANST | ||||||
Repeat | 151-181 | ANK 1 | ||||
Sequence: EGCTPLHLACRKGDSEILVELVQYCHAQMDV | ||||||
Repeat | 185-215 | ANK 2 | ||||
Sequence: KGETAFHYAVQGDNPQVLQLLGKNASAGLNQ | ||||||
Repeat | 219-248 | ANK 3 | ||||
Sequence: QGLTPLHLACQMGKQEMVRVLLLCNARCNI | ||||||
Repeat | 251-281 | ANK 4 | ||||
Sequence: PGGFPIHTAMKFSQKGCAEMIISMDSNQIHS | ||||||
Repeat | 286-312 | ANK 5 | ||||
Sequence: YGASPLHWAKNAEMARMLLKRGCDVDS | ||||||
Repeat | 316-345 | ANK 6 | ||||
Sequence: SGNTALHVAVTRNRFDCVMVLLTYGANAGA | ||||||
Repeat | 349-378 | ANK 7 | ||||
Sequence: HGNTPLHLAMSKDNMEMVKALIVFGAEVDT | ||||||
Repeat | 382-403 | ANK 9 | ||||
Sequence: FGETPAFIASKISKLITRKALL | ||||||
Domain | 482-666 | PNPLA | ||||
Sequence: LCLDGGGVKGLVIIQLLIAIEKASGVATKDLFDWVAGTSTGGILALAILHSKSMAYMRGVYFRMKDEVFRGSRPYESGPLEEFLKREFGEHTKMTDVKKPKVMLTGTLSDRQPAELHLFRNYDAPEAVREPRCTPNINLKPPTQPADQLVWRAARSSGAAPTYFRPNGRFLDGGLLANNPTLDAM | ||||||
Motif | 486-491 | GXGXXG | ||||
Sequence: GGGVKG | ||||||
Motif | 518-522 | GXSXG | ||||
Sequence: GTSTG | ||||||
Motif | 653-655 | DGA/G | ||||
Sequence: DGG | ||||||
Region | 678-687 | Calmodulin-binding (1-9-14 motif) | ||||
Sequence: RKGQGNKVKK | ||||||
Region | 749-760 | Calmodulin-binding (IQ motif) | ||||
Sequence: AWCEMVGIQYFR |
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).
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
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.
- NameLong
- Length807
- Mass (Da)89,556
- Last updated2012-10-31 v2
- Checksum1B9018AE1B2D252F
P97570-2
- NameShort
- Differences from canonical
- 396-451: LITRKALLTLLKTVGADYHFPFIQGVSTEQSSAAGPHPFFSLDRTQPPTISLNNLE → Q
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8L2Q8C9 | A0A8L2Q8C9_RAT | Pla2g6 | 770 | ||
A0A8L2Q8G5 | A0A8L2Q8G5_RAT | Pla2g6 | 844 | ||
A0A8L2R578 | A0A8L2R578_RAT | Pla2g6 | 760 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 24 | in Ref. 1; AAC53136 | ||||
Sequence: V → A | ||||||
Sequence conflict | 58 | in Ref. 1; AAC53136 | ||||
Sequence: V → D | ||||||
Sequence conflict | 68 | in Ref. 1; AAC53136 | ||||
Sequence: G → D | ||||||
Sequence conflict | 80 | in Ref. 1; AAC53136 | ||||
Sequence: A → V | ||||||
Sequence conflict | 99 | in Ref. 1; AAC53136 | ||||
Sequence: V → E | ||||||
Sequence conflict | 109 | in Ref. 1; AAC53136 | ||||
Sequence: Missing | ||||||
Sequence conflict | 142 | in Ref. 1; AAC53136 | ||||
Sequence: S → T | ||||||
Alternative sequence | VSP_044365 | 396-451 | in isoform Short | |||
Sequence: LITRKALLTLLKTVGADYHFPFIQGVSTEQSSAAGPHPFFSLDRTQPPTISLNNLE → Q | ||||||
Sequence conflict | 477 | in Ref. 1; AAC53136 | ||||
Sequence: S → T | ||||||
Sequence conflict | 793 | in Ref. 1; AAC53136 | ||||
Sequence: H → Y |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |