UniProtKB - Q9UNK4 (PA2GD_HUMAN)
Protein
Group IID secretory phospholipase A2
Gene
PLA2G2D
Organism
Homo sapiens (Human)
Status
Functioni
Secretory calcium-dependent phospholipase A2 that primarily targets extracellular lipids, exerting anti-inflammatory and immunosuppressive functions (PubMed:10455175, PubMed:10681567). 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). In draining lymph nodes, selectively hydrolyzes diacyl and alkenyl forms of phosphatidylethanolamines, releasing omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoate and docosahexaenoate that are precursors of the anti-inflammatory lipid mediators, resolvins (By similarity). During the resolution phase of acute inflammation drives docosahexaenoate-derived resolvin D1 synthesis, which suppresses dendritic cell activation and T-helper 1 immune response (By similarity). May act in an autocrine and paracrine manner (By similarity). Via a mechanism independent of its catalytic activity, promotes differentiation of regulatory T cells (Tregs) and participates in the maintenance of immune tolerance (By similarity). May contribute 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 (By similarity).By similarity2 Publications
Catalytic activityi
- a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + H2O = a 1-acyl-sn-glycero-3-phosphoethanolamine + a fatty acid + H+1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + 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+1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + H+ + hexadecanoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + H+1 PublicationThis reaction proceeds in the forward1 Publication direction.
- a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H+PROSITE-ProRule annotation2 PublicationsEC:3.1.1.4PROSITE-ProRule annotation2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+ + hexadecanoate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+2 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-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Ca2+1 PublicationNote: Binds 1 Ca2+ ion per subunit.
pH dependencei
Optimum pH is 7-9.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 47 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 49 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 51 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Active sitei | 67 | By similarity | 1 | |
Metal bindingi | 68 | CalciumBy similarity | 1 | |
Active sitei | 112 | By similarity | 1 |
GO - Molecular functioni
- calcium-dependent phospholipase A2 activity Source: UniProtKB
- calcium ion binding Source: GO_Central
- heparan sulfate proteoglycan binding Source: Ensembl
- heparin binding Source: Ensembl
- phospholipase A2 activity Source: ProtInc
- phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine) Source: UniProtKB-EC
- phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine) Source: UniProtKB-EC
- phospholipid binding Source: GO_Central
GO - Biological processi
- arachidonic acid secretion Source: InterPro
- CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation Source: Ensembl
- inflammatory response Source: ProtInc
- lipid catabolic process Source: UniProtKB-KW
- negative regulation of T cell proliferation Source: GO_Central
- phosphatidic acid biosynthetic process Source: Reactome
- 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
- phosphatidylinositol acyl-chain remodeling Source: Reactome
- phosphatidylserine acyl-chain remodeling Source: Reactome
- phospholipid metabolic process Source: GO_Central
- regulation of acute inflammatory response to antigenic stimulus Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid degradation, Lipid metabolism |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9UNK4 |
Reactomei | R-HSA-1482788, Acyl chain remodelling of PC R-HSA-1482801, Acyl chain remodelling of PS R-HSA-1482839, Acyl chain remodelling of PE R-HSA-1482922, Acyl chain remodelling of PI R-HSA-1482925, Acyl chain remodelling of PG R-HSA-1483166, Synthesis of PA |
Chemistry databases
SwissLipidsi | SLP:000000652 |
Names & Taxonomyi
Protein namesi | Recommended name: Group IID secretory phospholipase A2 (EC:3.1.1.42 Publications)Short name: GIID sPLA2 Short name: sPLA2-IID Alternative name(s): PLA2IID Phosphatidylcholine 2-acylhydrolase 2D Secretory-type PLA, stroma-associated homolog |
Gene namesi | Name:PLA2G2D Synonyms:SPLASH |
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
HGNCi | HGNC:9033, PLA2G2D |
MIMi | 605630, gene |
neXtProti | NX_Q9UNK4 |
VEuPathDBi | HostDB:ENSG00000117215.14 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: Reactome
Keywords - Cellular componenti
SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 26279 |
OpenTargetsi | ENSG00000117215 |
PharmGKBi | PA33363 |
Miscellaneous databases
Pharosi | Q9UNK4, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4281 |
DrugBanki | DB03017, Lauric acid DB03193, Stearic acid |
GuidetoPHARMACOLOGYi | 1418 |
Genetic variation databases
BioMutai | PLA2G2D |
DMDMi | 20139286 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
ChainiPRO_0000022755 | 21 – 145 | Group IID secretory phospholipase A2Add BLAST | 125 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 46 ↔ 138 | By similarity | ||
Disulfide bondi | 48 ↔ 64 | By similarity | ||
Disulfide bondi | 63 ↔ 118 | By similarity | ||
Disulfide bondi | 69 ↔ 145 | By similarity | ||
Disulfide bondi | 70 ↔ 111 | By similarity | ||
Disulfide bondi | 79 ↔ 104 | By similarity | ||
Glycosylationi | 89 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 97 ↔ 109 | By similarity |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | Q9UNK4 |
PaxDbi | Q9UNK4 |
PeptideAtlasi | Q9UNK4 |
PRIDEi | Q9UNK4 |
ProteomicsDBi | 85300 |
PTM databases
GlyGeni | Q9UNK4, 1 site |
iPTMneti | Q9UNK4 |
PhosphoSitePlusi | Q9UNK4 |
Expressioni
Tissue specificityi
Highly expressed in pancreas and spleen and less abundantly in colon, thymus, placenta, small intestine, and prostate.1 Publication
Gene expression databases
Bgeei | ENSG00000117215, Expressed in lymph node and 73 other tissues |
ExpressionAtlasi | Q9UNK4, baseline and differential |
Genevisiblei | Q9UNK4, HS |
Organism-specific databases
HPAi | ENSG00000117215, Tissue enriched (lymphoid) |
Interactioni
GO - Molecular functioni
- heparan sulfate proteoglycan binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 117662, 18 interactors |
STRINGi | 9606.ENSP00000364246 |
Chemistry databases
BindingDBi | Q9UNK4 |
Miscellaneous databases
RNActi | Q9UNK4, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the phospholipase A2 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4087, Eukaryota |
GeneTreei | ENSGT00940000161938 |
HOGENOMi | CLU_090683_3_0_1 |
InParanoidi | Q9UNK4 |
OMAi | DIHCSDK |
OrthoDBi | 1422829at2759 |
PhylomeDBi | Q9UNK4 |
TreeFami | TF319283 |
Family and domain databases
CDDi | cd00125, PLA2c, 1 hit |
Gene3Di | 1.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR001211, PLipase_A2 IPR033112, PLipase_A2_Asp_AS IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf IPR033113, PLipase_A2_His_AS |
PANTHERi | PTHR11716, PTHR11716, 1 hit |
Pfami | View protein in Pfam PF00068, Phospholip_A2_1, 1 hit |
PRINTSi | PR00389, PHPHLIPASEA2 |
SMARTi | View protein in SMART SM00085, PA2c, 1 hit |
SUPFAMi | SSF48619, SSF48619, 1 hit |
PROSITEi | View protein in PROSITE PS00119, PA2_ASP, 1 hit PS00118, PA2_HIS, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q9UNK4-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MELALLCGLV VMAGVIPIQG GILNLNKMVK QVTGKMPILS YWPYGCHCGL
60 70 80 90 100
GGRGQPKDAT DWCCQTHDCC YDHLKTQGCS IYKDYYRYNF SQGNIHCSDK
110 120 130 140
GSWCEQQLCA CDKEVAFCLK RNLDTYQKRL RFYWRPHCRG QTPGC
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_055387 | 65 | Q → H1 PublicationCorresponds to variant dbSNP:rs62541890Ensembl. | 1 | |
Natural variantiVAR_055388 | 73 | H → R1 PublicationCorresponds to variant dbSNP:rs62541891Ensembl. | 1 | |
Natural variantiVAR_012741 | 80 | S → G3 PublicationsCorresponds to variant dbSNP:rs584367Ensembl. | 1 | |
Natural variantiVAR_055389 | 96 | H → R1 PublicationCorresponds to variant dbSNP:rs62541892Ensembl. | 1 | |
Natural variantiVAR_055390 | 121 | R → C1 PublicationCorresponds to variant dbSNP:rs62541900Ensembl. | 1 | |
Natural variantiVAR_055391 | 121 | R → L1 PublicationCorresponds to variant dbSNP:rs62541901Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_060595 | 62 | W → C in isoform 2. | 1 | |
Alternative sequenceiVSP_060596 | 63 – 145 | Missing in isoform 2. Add BLAST | 83 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF112982 mRNA Translation: AAD51390.1 AF188625 mRNA Translation: AAF09020.1 AK290406 mRNA Translation: BAF83095.1 AK310156 mRNA No translation available. EU447440 Genomic DNA Translation: ACA06110.1 AL158172 Genomic DNA No translation available. BC025706 mRNA Translation: AAH25706.1 |
CCDSi | CCDS203.1 [Q9UNK4-1] CCDS72721.1 [Q9UNK4-2] |
RefSeqi | NP_001258743.1, NM_001271814.1 [Q9UNK4-2] NP_036532.1, NM_012400.3 [Q9UNK4-1] |
Genome annotation databases
Ensembli | ENST00000375105; ENSP00000364246; ENSG00000117215 [Q9UNK4-1] ENST00000617227; ENSP00000482871; ENSG00000117215 [Q9UNK4-2] |
GeneIDi | 26279 |
KEGGi | hsa:26279 |
UCSCi | uc001bcz.5, human [Q9UNK4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF112982 mRNA Translation: AAD51390.1 AF188625 mRNA Translation: AAF09020.1 AK290406 mRNA Translation: BAF83095.1 AK310156 mRNA No translation available. EU447440 Genomic DNA Translation: ACA06110.1 AL158172 Genomic DNA No translation available. BC025706 mRNA Translation: AAH25706.1 |
CCDSi | CCDS203.1 [Q9UNK4-1] CCDS72721.1 [Q9UNK4-2] |
RefSeqi | NP_001258743.1, NM_001271814.1 [Q9UNK4-2] NP_036532.1, NM_012400.3 [Q9UNK4-1] |
3D structure databases
SMRi | Q9UNK4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 117662, 18 interactors |
STRINGi | 9606.ENSP00000364246 |
Chemistry databases
BindingDBi | Q9UNK4 |
ChEMBLi | CHEMBL4281 |
DrugBanki | DB03017, Lauric acid DB03193, Stearic acid |
GuidetoPHARMACOLOGYi | 1418 |
SwissLipidsi | SLP:000000652 |
PTM databases
GlyGeni | Q9UNK4, 1 site |
iPTMneti | Q9UNK4 |
PhosphoSitePlusi | Q9UNK4 |
Genetic variation databases
BioMutai | PLA2G2D |
DMDMi | 20139286 |
Proteomic databases
MassIVEi | Q9UNK4 |
PaxDbi | Q9UNK4 |
PeptideAtlasi | Q9UNK4 |
PRIDEi | Q9UNK4 |
ProteomicsDBi | 85300 |
Protocols and materials databases
Antibodypediai | 47984, 186 antibodies |
DNASUi | 26279 |
Genome annotation databases
Ensembli | ENST00000375105; ENSP00000364246; ENSG00000117215 [Q9UNK4-1] ENST00000617227; ENSP00000482871; ENSG00000117215 [Q9UNK4-2] |
GeneIDi | 26279 |
KEGGi | hsa:26279 |
UCSCi | uc001bcz.5, human [Q9UNK4-1] |
Organism-specific databases
CTDi | 26279 |
DisGeNETi | 26279 |
GeneCardsi | PLA2G2D |
HGNCi | HGNC:9033, PLA2G2D |
HPAi | ENSG00000117215, Tissue enriched (lymphoid) |
MIMi | 605630, gene |
neXtProti | NX_Q9UNK4 |
OpenTargetsi | ENSG00000117215 |
PharmGKBi | PA33363 |
VEuPathDBi | HostDB:ENSG00000117215.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4087, Eukaryota |
GeneTreei | ENSGT00940000161938 |
HOGENOMi | CLU_090683_3_0_1 |
InParanoidi | Q9UNK4 |
OMAi | DIHCSDK |
OrthoDBi | 1422829at2759 |
PhylomeDBi | Q9UNK4 |
TreeFami | TF319283 |
Enzyme and pathway databases
PathwayCommonsi | Q9UNK4 |
Reactomei | R-HSA-1482788, Acyl chain remodelling of PC R-HSA-1482801, Acyl chain remodelling of PS R-HSA-1482839, Acyl chain remodelling of PE R-HSA-1482922, Acyl chain remodelling of PI R-HSA-1482925, Acyl chain remodelling of PG R-HSA-1483166, Synthesis of PA |
Miscellaneous databases
BioGRID-ORCSi | 26279, 7 hits in 983 CRISPR screens |
ChiTaRSi | PLA2G2D, human |
GeneWikii | PLA2G2D |
GenomeRNAii | 26279 |
Pharosi | Q9UNK4, Tchem |
PROi | PR:Q9UNK4 |
RNActi | Q9UNK4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000117215, Expressed in lymph node and 73 other tissues |
ExpressionAtlasi | Q9UNK4, baseline and differential |
Genevisiblei | Q9UNK4, HS |
Family and domain databases
CDDi | cd00125, PLA2c, 1 hit |
Gene3Di | 1.20.90.10, 1 hit |
InterProi | View protein in InterPro IPR001211, PLipase_A2 IPR033112, PLipase_A2_Asp_AS IPR016090, PLipase_A2_dom IPR036444, PLipase_A2_dom_sf IPR033113, PLipase_A2_His_AS |
PANTHERi | PTHR11716, PTHR11716, 1 hit |
Pfami | View protein in Pfam PF00068, Phospholip_A2_1, 1 hit |
PRINTSi | PR00389, PHPHLIPASEA2 |
SMARTi | View protein in SMART SM00085, PA2c, 1 hit |
SUPFAMi | SSF48619, SSF48619, 1 hit |
PROSITEi | View protein in PROSITE PS00119, PA2_ASP, 1 hit PS00118, PA2_HIS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PA2GD_HUMAN | |
Accessioni | Q9UNK4Primary (citable) accession number: Q9UNK4 Secondary accession number(s): A0A087WZT4 Q9UK01 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 11, 2002 |
Last sequence update: | February 11, 2002 | |
Last modified: | April 7, 2021 | |
This is version 174 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 chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families