Phospholipase A2, membrane associated

Details

Name
Phospholipase A2, membrane associated
Kind
protein
Synonyms
  • 3.1.1.4
  • GIIC sPLA2
  • Group IIA phospholipase A2
  • Non-pancreatic secretory phospholipase A2
  • NPS-PLA2
  • Phosphatidylcholine 2-acylhydrolase 2A
  • PLA2B
  • PLA2L
  • RASF-A
Gene Name
PLA2G2A
UniProtKB Entry
P14555Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0016509|Phospholipase A2, membrane associated
MKTLLLLAVIMIFGLLQAHGNLVNFHRMIKLTTGKEAALSYGFYGCHCGVGGRGSPKDAT
DRCCVTHDCCYKRLEKRGCGTKFLSYKFSNSGSRITCAKQDSCRSQLCECDKAAATCFAR
NKTTYNKKYQYYSNKHCRGSTPRC
Number of residues
144
Molecular Weight
16082.525
Theoretical pI
9.51
GO Classification
Processes
arachidonic acid secretion / inflammatory response / intestinal stem cell homeostasis / killing of cells of another organism / negative regulation of T cell proliferation / phosphatidylcholine metabolic process / phosphatidylethanolamine metabolic process / regulation of neutrophil activation
Components
mitochondrial outer membrane / plasma membrane
General Function
Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:10455175, PubMed:10681567, PubMed:2925633). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:10455175, PubMed:10681567). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:10358193, PubMed:11694541). Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response (PubMed:25082876). Plays a stem cell regulator role in the intestinal crypt. Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (PubMed:14998370). Independent of its catalytic activity, acts as a ligand for integrins (PubMed:18635536, PubMed:25398877). Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 (PubMed:18635536, PubMed:25398877). Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:25398877). Induces cell proliferation in an integrin-dependent manner (PubMed:18635536)
Specific Function
calcium ion binding
Pfam Domain Function
Signal Regions
1-20
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0016510|Phospholipase A2, membrane associated (PLA2G2A)
ATGAAGACCCTCCTACTGTTGGCAGTGATCATGATCTTTGGCCTACTGCAGGCCCATGGG
AATTTGGTGAATTTCCACAGAATGATCAAGTTGACGACAGGAAAGGAAGCCGCACTCAGT
TATGGCTTCTACGGCTGCCACTGTGGCGTGGGTGGCAGAGGATCCCCCAAGGATGCAACG
GATCGCTGCTGTGTCACTCATGACTGTTGCTACAAACGTCTGGAGAAACGTGGATGTGGC
ACCAAATTTCTGAGCTACAAGTTTAGCAACTCGGGGAGCAGAATCACCTGTGCAAAACAG
GACTCCTGCAGAAGTCAACTGTGTGAGTGTGATAAGGCTGCTGCCACCTGTTTTGCTAGA
AACAAGACGACCTACAATAAAAAGTACCAGTACTATTCCAATAAACACTGCAGAGGGAGC
ACCCCTCGTTGCTGA
Chromosome Location
1
Locus
1p36.13
External Identifiers
ResourceLink
UniProtKB IDP14555
UniProtKB Entry NamePA2GA_HUMAN
GenBank Protein ID190889
GenBank Gene IDM22430
GeneCard IDPLA2G2A
GenAtlas IDPLA2G2A
HGNC IDHGNC:9031
PDB ID(s)1AYP, 1BBC, 1DB4, 1DB5, 1DCY, 1J1A, 1KQU, 1KVO, 1N28, 1N29, 1POD, 1POE, 3U8B, 3U8D, 3U8H, 3U8I, 5G3N
KEGG IDhsa:5320
IUPHAR/Guide To Pharmacology ID1417
NCBI Gene ID5320
General References
  1. Seilhamer JJ, Pruzanski W, Vadas P, Plant S, Miller JA, Kloss J, Johnson LK: Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. J Biol Chem. 1989 Apr 5;264(10):5335-8. [Article]
  2. Kramer RM, Hession C, Johansen B, Hayes G, McGray P, Chow EP, Tizard R, Pepinsky RB: Structure and properties of a human non-pancreatic phospholipase A2. J Biol Chem. 1989 Apr 5;264(10):5768-75. [Article]
  3. Kramer RM, Johansen B, Hession C, Pepinsky RB: Structure and properties of a secretable phospholipase A2 from human platelets. Adv Exp Med Biol. 1990;275:35-53. [Article]
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  7. Kanda A, Ono T, Yoshida N, Tojo H, Okamoto M: The primary structure of a membrane-associated phospholipase A2 from human spleen. Biochem Biophys Res Commun. 1989 Aug 30;163(1):42-8. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
1,4-ButanediolexperimentalyestargetinhibitorDetails
[3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic AcidexperimentalunknowntargetDetails
4-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Butyric AcidexperimentalunknowntargetDetails
(1-Benzyl-5-methoxy-2-methyl-1H-indol-3-yl)acetic acidexperimentalunknowntargetDetails
6-phenyl-4(R)-(7-phenyl-heptanoylamino)-hexanoic acidexperimentalunknowntargetDetails
ElaidamideexperimentalunknowntargetDetails
(2R)-2-Acetamido-3-(octadecyloxy)propyl 2-(methylsulfanyl)ethyl hydrogen phosphateexperimentalunknowntargetDetails
KH064experimentalyestargetinhibitorDetails
SuramininvestigationalunknowntargetinhibitorDetails
Varespladib methylinvestigationalunknowntargetDetails
Indomethacinapproved, investigationalyestargetinhibitorDetails
Ginkgo bilobaapproved, investigational, nutraceuticalunknowntargetinhibitorDetails
Lauric acidapproved, experimentalyestargetinhibitorDetails
N-Tridecanoic AcidexperimentalyestargetinhibitorDetails
1-{2-[2-(2-Methoxyethoxy)Ethoxy]Ethoxy}-4-(1,1,3,3-Tetramethylbutyl)BenzeneexperimentalunknowntargetDetails
Diclofenacapproved, vet_approvedunknownenzymeinhibitorDetails
Isopropyl alcoholapproved, investigationalyestargetinhibitorDetails