UniProtKB - Q9NZ20 (PA2G3_HUMAN)
Protein
Group 3 secretory phospholipase A2
Gene
PLA2G3
Organism
Homo sapiens (Human)
Status
Functioni
Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids without apparent head group selectivity (PubMed:12522102, PubMed:18801741, PubMed:15863501, PubMed:28947740). Contributes to phospholipid remodeling of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells (PubMed:18801741). May act in an autocrine and paracrine manner (PubMed:23624557). Secreted by immature mast cells, acts on nearby fibroblasts upstream to PTDGS to synthesize prostaglandin D2 (PGD2), which in turn promotes mast cell maturation and degranulation via PTGDR (PubMed:23624557). Secreted by epididymal epithelium, acts on immature sperm cells within the duct, modulating the degree of unsaturation of the fatty acyl components of phosphatidylcholines required for acrosome assembly and sperm cell motility. Facilitates the replacement of fatty acyl chains in phosphatidylcholines in sperm membranes from omega-6 and omega-9 to omega-3 polyunsaturated fatty acids (PUFAs). Coupled to lipoxygenase pathway, may process omega-6 PUFAs to generate oxygenated lipid mediators in the male reproductive tract (By similarity). At pericentrosomal preciliary compartment, negatively regulates ciliogenesis likely by regulating endocytotic recycling of ciliary membrane protein (PubMed:20393563). Coupled to cyclooxygenase pathway provides arachidonate to generate prostaglandin E2 (PGE2), a potent immunomodulatory lipid in inflammation and tumorigenesis (PubMed:12522102, PubMed:15863501). At colonic epithelial barrier, preferentially hydrolyzes phospholipids having arachidonate and docosahexaenoate at sn-2 position, contributing to the generation of oxygenated metabolites involved in colonic stem cell homeostasis (PubMed:28947740). Releases C16:0 and C18:0 lysophosphatidylcholine subclasses from neuron plasma membranes and promotes neurite outgrowth and neuron survival (PubMed:17868035).By similarity7 Publications
Catalytic activityi
- a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H+2 PublicationsEC:3.1.1.42 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+1 PublicationThis reaction proceeds in the forward1 Publication 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+1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + H+4 PublicationsThis reaction proceeds in the forward4 Publications 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+1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Ca2+By similarityNote: Binds 1 Ca2+ ion.By similarity
Activity regulationi
Arachidonic acid release is markedly increased by glypican, a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 158 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 160 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 162 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Active sitei | 184 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 185 | CalciumBy similarity | 1 | |
Active sitei | 214 | By similarity | 1 |
GO - Molecular functioni
- calcium-dependent phospholipase A2 activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine) Source: UniProtKB-EC
- phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine) Source: UniProtKB-EC
GO - Biological processi
- acrosome assembly Source: Ensembl
- age-dependent response to oxidative stress involved in chronological cell aging Source: Ensembl
- arachidonic acid secretion Source: InterPro
- cell maturation Source: Ensembl
- cilium assembly Source: UniProtKB
- high-density lipoprotein particle remodeling Source: UniProtKB
- lipoxygenase pathway Source: Ensembl
- low-density lipoprotein particle remodeling Source: UniProtKB
- macrophage activation Source: Ensembl
- mast cell degranulation Source: UniProtKB-KW
- negative regulation of amyloid-beta clearance Source: Ensembl
- negative regulation of gene expression Source: MGI
- negative regulation of neuron apoptotic process Source: UniProtKB
- phosphatidic acid metabolic process Source: UniProtKB
- phosphatidylcholine acyl-chain remodeling Source: Reactome
- phosphatidylcholine metabolic process Source: UniProtKB
- phosphatidylethanolamine acyl-chain remodeling Source: Reactome
- phosphatidylethanolamine metabolic process Source: UniProtKB
- phosphatidylglycerol acyl-chain remodeling Source: Reactome
- phosphatidylglycerol metabolic process Source: UniProtKB
- phosphatidylinositol metabolic process Source: UniProtKB
- phosphatidylserine metabolic process Source: UniProtKB
- phospholipid metabolic process Source: ProtInc
- positive regulation of cytokine production involved in inflammatory response Source: Ensembl
- positive regulation of histamine secretion by mast cell Source: UniProtKB
- positive regulation of macrophage derived foam cell differentiation Source: UniProtKB
- positive regulation of mast cell differentiation Source: Ensembl
- positive regulation of neuron projection development Source: UniProtKB
- positive regulation of prostaglandin biosynthetic process Source: UniProtKB
- positive regulation of prostaglandin secretion Source: Ensembl
- production of molecular mediator involved in inflammatory response Source: Ensembl
- regulation of endocytic recycling Source: UniProtKB
- sperm axoneme assembly Source: Ensembl
Keywordsi
Molecular function | Hydrolase |
Biological process | Cilium biogenesis/degradation, Lipid metabolism, Mast cell degranulation, Phospholipid metabolism |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9NZ20 |
Reactomei | R-HSA-1482788, Acyl chain remodelling of PC R-HSA-1482839, Acyl chain remodelling of PE R-HSA-1482925, Acyl chain remodelling of PG |
Chemistry databases
SwissLipidsi | SLP:000001086 |
Names & Taxonomyi
Protein namesi | Recommended name: Group 3 secretory phospholipase A2 (EC:3.1.1.42 Publications)Alternative name(s): Group III secretory phospholipase A2 Short name: GIII sPLA2 Short name: sPLA2-III Phosphatidylcholine 2-acylhydrolase 3 |
Gene namesi | Name:PLA2G3Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000100078.3 |
HGNCi | HGNC:17934, PLA2G3 |
MIMi | 611651, gene |
neXtProti | NX_Q9NZ20 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication
Extracellular region or secreted
- Secreted 1 Publication
Cytoskeleton
- centriole 1 Publication
Endosome
- Recycling endosome 1 Publication
Note: Localized at pericentrosomal preciliary compartment.1 Publication
Cytoskeleton
- centriole Source: UniProtKB
Endosome
- recycling endosome Source: UniProtKB
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: ProtInc
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoskeleton, Endosome, Membrane, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 167 | N → S: Loss of glycosylation. 1 Publication | 1 | |
Mutagenesisi | 184 | H → Q: Impairs PGE2 synthesis. Impairs PGD2 synthesis. Impairs mast cell degranulation. Impairs neurite outgrowth. 4 Publications | 1 | |
Mutagenesisi | 280 | N → S: Loss of glycosylation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 50487 |
OpenTargetsi | ENSG00000100078 |
PharmGKBi | PA38267 |
Miscellaneous databases
Pharosi | Q9NZ20, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4667 |
Polymorphism and mutation databases
BioMutai | PLA2G3 |
DMDMi | 317373314 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Sequence analysisAdd BLAST | 19 | |
ChainiPRO_0000022992 | 20 – 509 | Group 3 secretory phospholipase A2Sequence analysisAdd BLAST | 490 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 159 ↔ 181 | By similarity | ||
Glycosylationi | 167 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 180 ↔ 220 | By similarity | ||
Disulfide bondi | 187 ↔ 213 | By similarity | ||
Disulfide bondi | 211 ↔ 244 | By similarity | ||
Glycosylationi | 280 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 325 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 396 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 439 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
N-glycosylation does not affect the catalytic activity, but is required for proper secretion. A nonglycosylated form is observed in several cell types.1 Publication
In several cell types, the N- and C-termini are cleaved off.1 Publication
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | Q9NZ20 |
MassIVEi | Q9NZ20 |
PaxDbi | Q9NZ20 |
PeptideAtlasi | Q9NZ20 |
PRIDEi | Q9NZ20 |
ProteomicsDBi | 83316 |
PTM databases
GlyGeni | Q9NZ20, 5 sites |
iPTMneti | Q9NZ20 |
PhosphoSitePlusi | Q9NZ20 |
Expressioni
Tissue specificityi
Expressed in kidney, heart, liver, and skeletal muscle. Also present in placenta and peripheral blood leukocytes. Not detected in colon, thymus, spleen and small intestine. In lung, expressed in bronchial epithelial cells and alveolar macrophages, but scarcely detected in alveolar epithelium, arterial walls and interstitial fibroblasts (at protein level). In joints of osteoarthritis and rheumatoid arthritis, expressed in endothelial cells (at protein level). In normal heart, detected in some vessels. In myocardial tissues with acute infarction, expressed in vascular endothelial cells adjacent to cardiomyocytes and those in lesions with granulation. Expression in cardiomyocytes is scarce (at protein level). In uterus, breast and colon cancers, detected in tumor cells and neighboring microvascular endothelium, but not in normal glandular tissues (at protein level) (PubMed:15863501). Expressed in dermal resting mast cells (at protein level) and pulmonary mast cells (PubMed:23624557). Expressed in neuronal fibers (at protein level) (PubMed:17868035). Highly expressed in dorsal root ganglia neurons (at protein level) (PubMed:17868035). Expressed in Purkinje cells in cerebellum (at protein level) (PubMed:17868035). In stomach is preferentially expressed in neuronal fibers and in microvascular endothelium (PubMed:17868035). Sparsely expressed in normal aorta (at protein level). Highly expressed in macrophages and smooth muscle cells in aorta with atheroma (PubMed:18801741).4 Publications
Inductioni
By IL1B/interleukin-1 beta and TNF in microvascular endothelial cells (at protein level).1 Publication
Gene expression databases
Bgeei | ENSG00000100078, Expressed in ectocervix and 97 other tissues |
Genevisiblei | Q9NZ20, HS |
Organism-specific databases
HPAi | ENSG00000100078, Tissue enhanced (esophagus, skin, tongue) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 119074, 2 interactors |
IntActi | Q9NZ20, 2 interactors |
STRINGi | 9606.ENSP00000215885 |
Miscellaneous databases
RNActi | Q9NZ20, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 150 – 291 | Phospholipase A2-like3 PublicationsAdd BLAST | 142 |
Domaini
The phospholipase A2-like domain represents the fully processed form after N- and C-termini are cleaved off. It is the secreted mature form found in biological fluids.3 Publications
Sequence similaritiesi
Belongs to the phospholipase A2 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502QTYI, Eukaryota |
GeneTreei | ENSGT00940000161662 |
HOGENOMi | CLU_535922_0_0_1 |
InParanoidi | Q9NZ20 |
OMAi | CPQNISP |
OrthoDBi | 893757at2759 |
PhylomeDBi | Q9NZ20 |
TreeFami | TF324679 |
Family and domain databases
Gene3Di | 1.20.90.10, 2 hits |
InterProi | View protein in InterPro IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf IPR033113, PLipase_A2_His_AS |
Pfami | View protein in Pfam PF05826, Phospholip_A2_2, 1 hit |
SUPFAMi | SSF48619, SSF48619, 2 hits |
PROSITEi | View protein in PROSITE PS00118, PA2_HIS, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q9NZ20-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGVQAGLFGM LGFLGVALGG SPALRWYRTS CHLTKAVPGN PLGYLSFLAK
60 70 80 90 100
DAQGLALIHA RWDAHRRLQS CSWEDEPELT AAYGALCAHE TAWGSFIHTP
110 120 130 140 150
GPELQRALAT LQSQWEACRA LEESPAGARK KRAAGQSGVP GGGHQREKRG
160 170 180 190 200
WTMPGTLWCG VGDSAGNSSE LGVFQGPDLC CREHDRCPQN ISPLQYNYGI
210 220 230 240 250
RNYRFHTISH CDCDTRFQQC LQNQHDSISD IVGVAFFNVL EIPCFVLEEQ
260 270 280 290 300
EACVAWYWWG GCRMYGTVPL ARLQPRTFYN ASWSSRATSP TPSSRSPAPP
310 320 330 340 350
KPRQKQHLRK GPPHQKGSKR PSKANTTALQ DPMVSPRLDV APTGLQGPQG
360 370 380 390 400
GLKPQGARWV CRSFRRHLDQ CEHQIGPREI EFQLLNSAQE PLFHCNCTRR
410 420 430 440 450
LARFLRLHSP PEVTNMLWEL LGTTCFKLAP PLDCVEGKNC SRDPRAIRVS
460 470 480 490 500
ARHLRRLQQR RHQLQDKGTD ERQPWPSEPL RGPMSFYNQC LQLTQAARRP
DRQQKSWSQ
Sequence cautioni
The sequence AAD15617 differs from that shown. Reason: Erroneous gene model prediction.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024555 | 70 | S → A2 PublicationsCorresponds to variant dbSNP:rs2232176Ensembl. | 1 | |
Natural variantiVAR_024556 | 116 | E → Q. Corresponds to variant dbSNP:rs2074734Ensembl. | 1 | |
Natural variantiVAR_020288 | 157 | L → V. Corresponds to variant dbSNP:rs2074735Ensembl. | 1 | |
Natural variantiVAR_056581 | 307 | H → Y. Corresponds to variant dbSNP:rs2232180Ensembl. | 1 | |
Natural variantiVAR_024557 | 322 | S → R. Corresponds to variant dbSNP:rs2072193Ensembl. | 1 | |
Natural variantiVAR_034366 | 378 | R → Q. Corresponds to variant dbSNP:rs2232183Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF220490 mRNA Translation: AAF44746.1 AC005005 Genomic DNA Translation: AAD15617.1 Sequence problems. BC025316 mRNA Translation: AAH25316.1 |
CCDSi | CCDS13889.1 |
RefSeqi | NP_056530.2, NM_015715.4 |
Genome annotation databases
Ensembli | ENST00000215885; ENSP00000215885; ENSG00000100078 |
GeneIDi | 50487 |
KEGGi | hsa:50487 |
UCSCi | uc003aka.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF220490 mRNA Translation: AAF44746.1 AC005005 Genomic DNA Translation: AAD15617.1 Sequence problems. BC025316 mRNA Translation: AAH25316.1 |
CCDSi | CCDS13889.1 |
RefSeqi | NP_056530.2, NM_015715.4 |
3D structure databases
SMRi | Q9NZ20 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 119074, 2 interactors |
IntActi | Q9NZ20, 2 interactors |
STRINGi | 9606.ENSP00000215885 |
Chemistry databases
ChEMBLi | CHEMBL4667 |
SwissLipidsi | SLP:000001086 |
PTM databases
GlyGeni | Q9NZ20, 5 sites |
iPTMneti | Q9NZ20 |
PhosphoSitePlusi | Q9NZ20 |
Polymorphism and mutation databases
BioMutai | PLA2G3 |
DMDMi | 317373314 |
Proteomic databases
EPDi | Q9NZ20 |
MassIVEi | Q9NZ20 |
PaxDbi | Q9NZ20 |
PeptideAtlasi | Q9NZ20 |
PRIDEi | Q9NZ20 |
ProteomicsDBi | 83316 |
Protocols and materials databases
Antibodypediai | 11027, 183 antibodies |
DNASUi | 50487 |
Genome annotation databases
Ensembli | ENST00000215885; ENSP00000215885; ENSG00000100078 |
GeneIDi | 50487 |
KEGGi | hsa:50487 |
UCSCi | uc003aka.4, human |
Organism-specific databases
CTDi | 50487 |
DisGeNETi | 50487 |
EuPathDBi | HostDB:ENSG00000100078.3 |
GeneCardsi | PLA2G3 |
HGNCi | HGNC:17934, PLA2G3 |
HPAi | ENSG00000100078, Tissue enhanced (esophagus, skin, tongue) |
MIMi | 611651, gene |
neXtProti | NX_Q9NZ20 |
OpenTargetsi | ENSG00000100078 |
PharmGKBi | PA38267 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QTYI, Eukaryota |
GeneTreei | ENSGT00940000161662 |
HOGENOMi | CLU_535922_0_0_1 |
InParanoidi | Q9NZ20 |
OMAi | CPQNISP |
OrthoDBi | 893757at2759 |
PhylomeDBi | Q9NZ20 |
TreeFami | TF324679 |
Enzyme and pathway databases
PathwayCommonsi | Q9NZ20 |
Reactomei | R-HSA-1482788, Acyl chain remodelling of PC R-HSA-1482839, Acyl chain remodelling of PE R-HSA-1482925, Acyl chain remodelling of PG |
Miscellaneous databases
BioGRID-ORCSi | 50487, 3 hits in 844 CRISPR screens |
GenomeRNAii | 50487 |
Pharosi | Q9NZ20, Tbio |
PROi | PR:Q9NZ20 |
RNActi | Q9NZ20, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000100078, Expressed in ectocervix and 97 other tissues |
Genevisiblei | Q9NZ20, HS |
Family and domain databases
Gene3Di | 1.20.90.10, 2 hits |
InterProi | View protein in InterPro IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf IPR033113, PLipase_A2_His_AS |
Pfami | View protein in Pfam PF05826, Phospholip_A2_2, 1 hit |
SUPFAMi | SSF48619, SSF48619, 2 hits |
PROSITEi | View protein in PROSITE PS00118, PA2_HIS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PA2G3_HUMAN | |
Accessioni | Q9NZ20Primary (citable) accession number: Q9NZ20 Secondary accession number(s): O95768 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 11, 2002 |
Last sequence update: | January 11, 2011 | |
Last modified: | December 2, 2020 | |
This is version 163 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations