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Protein

Phospholipase A2, membrane associated

Gene

PLA2G2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides (PubMed:2925633). Thought to participate in the regulation of phospholipid metabolism in biomembranes including eicosanoid biosynthesis. 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).3 Publications

Miscellaneous

Group II phospholipase A2 is found in many cells and also extracellularly. The membrane-bound and secreted forms are identical and are encoded by a single gene.
Interaction with integrin ITGA4:ITGB3 is inhibited by a number of synthetic peptides including R-Ala-Trp-Asp-Ile and R-Gly-Arg-Gly-Asp-Asp-Asp which bind to PLA2G2A and disrupt its integrin-binding activity.1 Publication

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.PROSITE-ProRule annotation1 Publication

Cofactori

Ca2+1 PublicationNote: Binds 1 Ca2+ ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi47Calcium; via carbonyl oxygen1
Metal bindingi49Calcium; via carbonyl oxygen1
Metal bindingi51Calcium; via carbonyl oxygen1
Active sitei67By similarity1
Metal bindingi68Calcium1
Sitei94Important for integrin binding1 Publication1
Active sitei111By similarity1
Sitei120Important for integrin binding1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processLipid degradation, Lipid metabolism
LigandCalcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.1.4 2681
ReactomeiR-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
R-HSA-6803157 Antimicrobial peptides

Chemistry databases

SwissLipidsiSLP:000000653

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipase A2, membrane associated (EC:3.1.1.41 Publication)
Alternative name(s):
GIIC sPLA2
Group IIA phospholipase A2
Non-pancreatic secretory phospholipase A2
Short name:
NPS-PLA2
Phosphatidylcholine 2-acylhydrolase 2A
Gene namesi
Name:PLA2G2A
Synonyms:PLA2B, PLA2L, RASF-A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000188257.10
HGNCiHGNC:9031 PLA2G2A
MIMi172411 gene
neXtProtiNX_P14555

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49G → S: No effect on integrin binding; when associated with K-68. 1 Publication1
Mutagenesisi62R → E: No effect on integrin binding. 1 Publication1
Mutagenesisi67H → Q: Catalytically inactive but does not affect integrin binding. 2 Publications1
Mutagenesisi68D → K: No effect on integrin binding; when associated with S-49. 1 Publication1
Mutagenesisi73R → E: Slightly reduced integrin binding. 1 Publication1
Mutagenesisi94R → E: Moderately reduced integrin binding. Greatly reduced integrin binding but no effect on catalytic activity; when associated with E-120. 2 Publications1
Mutagenesisi120R → E: Moderately reduced integrin binding. Greatly reduced integrin binding but no effect on catalytic activity; when associated with E-94. 2 Publications1

Organism-specific databases

DisGeNETi5320
MalaCardsiPLA2G2A
OpenTargetsiENSG00000188257
PharmGKBiPA270

Chemistry databases

ChEMBLiCHEMBL3474
DrugBankiDB04287 (S)-5-(4-Benzyloxy-Phenyl)-4-(7-Phenyl-Heptanoylamino)-Pentanoic Acid
DB03121 1-Benzyl-5-Methoxy-2-Methyl-1h-Indol-3-Yl)-Acetic Acid
DB04112 1-Octadecyl-2-Acetamido-2-Deoxy-Sn-Glycerol-3-Phosphoethylmethyl Sulfide
DB02936 4-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Butyric Acid
DB03471 6-Phenyl-4(R)-(7-Phenyl-Heptanoylamino)-Hexanoic Acid
DB02504 [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid
DB00586 Diclofenac
DB03784 Elaidoylamide
DB01381 Ginkgo biloba
DB00328 Indomethacin
DB02325 Isopropyl Alcohol
DB03017 Lauric Acid
DB02448 N-Tridecanoic Acid
DB04786 Suramin
GuidetoPHARMACOLOGYi1417

Polymorphism and mutation databases

BioMutaiPLA2G2A
DMDMi129483

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 205 PublicationsAdd BLAST20
ChainiPRO_000002275021 – 144Phospholipase A2, membrane associatedAdd BLAST124

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi46 ↔ 137
Disulfide bondi48 ↔ 64
Disulfide bondi63 ↔ 117
Disulfide bondi69 ↔ 144
Disulfide bondi70 ↔ 110
Disulfide bondi79 ↔ 103
Disulfide bondi97 ↔ 108

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiP14555
PaxDbiP14555
PeptideAtlasiP14555
PRIDEiP14555
ProteomicsDBi53059

PTM databases

iPTMnetiP14555
PhosphoSitePlusiP14555

Expressioni

Gene expression databases

BgeeiENSG00000188257 Expressed in 171 organ(s), highest expression level in tendon
CleanExiHS_PLA2G2A
ExpressionAtlasiP14555 baseline and differential
GenevisibleiP14555 HS

Organism-specific databases

HPAiHPA015236

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ITGB3P051063EBI-16414951,EBI-702847

Protein-protein interaction databases

BioGridi111337, 26 interactors
IntActiP14555, 6 interactors
MINTiP14555
STRINGi9606.ENSP00000364252

Chemistry databases

BindingDBiP14555

Structurei

Secondary structure

1144
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP14555
SMRiP14555
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14555

Family & Domainsi

Sequence similaritiesi

Belongs to the phospholipase A2 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4087 Eukaryota
ENOG411283D LUCA
GeneTreeiENSGT00760000119160
HOGENOMiHOG000231749
HOVERGENiHBG008137
InParanoidiP14555
KOiK01047
OMAiKYQFYPN
OrthoDBiEOG091G0UZ3
PhylomeDBiP14555
TreeFamiTF319283

Family and domain databases

CDDicd00125 PLA2c, 1 hit
Gene3Di1.20.90.10, 1 hit
InterProiView 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
PANTHERiPTHR11716 PTHR11716, 1 hit
PfamiView protein in Pfam
PF00068 Phospholip_A2_1, 1 hit
PRINTSiPR00389 PHPHLIPASEA2
SMARTiView protein in SMART
SM00085 PA2c, 1 hit
SUPFAMiSSF48619 SSF48619, 1 hit
PROSITEiView protein in PROSITE
PS00119 PA2_ASP, 1 hit
PS00118 PA2_HIS, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P14555-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKTLLLLAVI MIFGLLQAHG NLVNFHRMIK LTTGKEAALS YGFYGCHCGV
60 70 80 90 100
GGRGSPKDAT DRCCVTHDCC YKRLEKRGCG TKFLSYKFSN SGSRITCAKQ
110 120 130 140
DSCRSQLCEC DKAAATCFAR NKTTYNKKYQ YYSNKHCRGS TPRC
Length:144
Mass (Da):16,083
Last modified:April 1, 1990 - v2
Checksum:i923C5FA0C6979CDA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12I → Y in AAT73043 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01895319H → Y1 PublicationCorresponds to variant dbSNP:rs11573162Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22430 mRNA Translation: AAA36550.1
M22431 Genomic DNA Translation: AAA36549.1
AY656695 mRNA Translation: AAT73043.1
CR456865 mRNA Translation: CAG33146.1
AY462114 Genomic DNA Translation: AAR16084.1
AL358253 Genomic DNA No translation available.
AK291302 mRNA Translation: BAF83991.1
CH471134 Genomic DNA Translation: EAW94907.1
BC005919 mRNA Translation: AAH05919.1
CCDSiCCDS201.1
PIRiA32862 PSHUYF
RefSeqiNP_000291.1, NM_000300.3
NP_001155199.1, NM_001161727.1
NP_001155200.1, NM_001161728.1
NP_001155201.1, NM_001161729.1
UniGeneiHs.466804

Genome annotation databases

EnsembliENST00000375111; ENSP00000364252; ENSG00000188257
ENST00000400520; ENSP00000383364; ENSG00000188257
GeneIDi5320
KEGGihsa:5320
UCSCiuc001bcv.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22430 mRNA Translation: AAA36550.1
M22431 Genomic DNA Translation: AAA36549.1
AY656695 mRNA Translation: AAT73043.1
CR456865 mRNA Translation: CAG33146.1
AY462114 Genomic DNA Translation: AAR16084.1
AL358253 Genomic DNA No translation available.
AK291302 mRNA Translation: BAF83991.1
CH471134 Genomic DNA Translation: EAW94907.1
BC005919 mRNA Translation: AAH05919.1
CCDSiCCDS201.1
PIRiA32862 PSHUYF
RefSeqiNP_000291.1, NM_000300.3
NP_001155199.1, NM_001161727.1
NP_001155200.1, NM_001161728.1
NP_001155201.1, NM_001161729.1
UniGeneiHs.466804

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AYPX-ray2.57A/B/C/D/E/F21-144[»]
1BBCX-ray2.20A21-144[»]
1DB4X-ray2.20A21-144[»]
1DB5X-ray2.80A21-144[»]
1DCYX-ray2.70A21-144[»]
1J1AX-ray2.20A/B21-144[»]
1KQUX-ray2.10A21-144[»]
1KVOX-ray2.00A/B/C/D/E/F21-144[»]
1N28X-ray1.50A/B21-144[»]
1N29X-ray2.60A21-144[»]
1PODX-ray2.10A21-144[»]
1POEX-ray2.10A/B21-144[»]
2GNYmodel-A21-144[»]
3U8BX-ray2.30A21-144[»]
3U8DX-ray1.80A/B21-144[»]
3U8HX-ray2.30A/B21-144[»]
3U8IX-ray1.10A/B21-144[»]
5G3NX-ray1.80A/B21-144[»]
ProteinModelPortaliP14555
SMRiP14555
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111337, 26 interactors
IntActiP14555, 6 interactors
MINTiP14555
STRINGi9606.ENSP00000364252

Chemistry databases

BindingDBiP14555
ChEMBLiCHEMBL3474
DrugBankiDB04287 (S)-5-(4-Benzyloxy-Phenyl)-4-(7-Phenyl-Heptanoylamino)-Pentanoic Acid
DB03121 1-Benzyl-5-Methoxy-2-Methyl-1h-Indol-3-Yl)-Acetic Acid
DB04112 1-Octadecyl-2-Acetamido-2-Deoxy-Sn-Glycerol-3-Phosphoethylmethyl Sulfide
DB02936 4-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Butyric Acid
DB03471 6-Phenyl-4(R)-(7-Phenyl-Heptanoylamino)-Hexanoic Acid
DB02504 [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid
DB00586 Diclofenac
DB03784 Elaidoylamide
DB01381 Ginkgo biloba
DB00328 Indomethacin
DB02325 Isopropyl Alcohol
DB03017 Lauric Acid
DB02448 N-Tridecanoic Acid
DB04786 Suramin
GuidetoPHARMACOLOGYi1417
SwissLipidsiSLP:000000653

PTM databases

iPTMnetiP14555
PhosphoSitePlusiP14555

Polymorphism and mutation databases

BioMutaiPLA2G2A
DMDMi129483

Proteomic databases

EPDiP14555
PaxDbiP14555
PeptideAtlasiP14555
PRIDEiP14555
ProteomicsDBi53059

Protocols and materials databases

DNASUi5320
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375111; ENSP00000364252; ENSG00000188257
ENST00000400520; ENSP00000383364; ENSG00000188257
GeneIDi5320
KEGGihsa:5320
UCSCiuc001bcv.4 human

Organism-specific databases

CTDi5320
DisGeNETi5320
EuPathDBiHostDB:ENSG00000188257.10
GeneCardsiPLA2G2A
HGNCiHGNC:9031 PLA2G2A
HPAiHPA015236
MalaCardsiPLA2G2A
MIMi172411 gene
neXtProtiNX_P14555
OpenTargetsiENSG00000188257
PharmGKBiPA270
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4087 Eukaryota
ENOG411283D LUCA
GeneTreeiENSGT00760000119160
HOGENOMiHOG000231749
HOVERGENiHBG008137
InParanoidiP14555
KOiK01047
OMAiKYQFYPN
OrthoDBiEOG091G0UZ3
PhylomeDBiP14555
TreeFamiTF319283

Enzyme and pathway databases

BRENDAi3.1.1.4 2681
ReactomeiR-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
R-HSA-6803157 Antimicrobial peptides

Miscellaneous databases

ChiTaRSiPLA2G2A human
EvolutionaryTraceiP14555
GeneWikiiPLA2G2A
GenomeRNAii5320
PROiPR:P14555
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188257 Expressed in 171 organ(s), highest expression level in tendon
CleanExiHS_PLA2G2A
ExpressionAtlasiP14555 baseline and differential
GenevisibleiP14555 HS

Family and domain databases

CDDicd00125 PLA2c, 1 hit
Gene3Di1.20.90.10, 1 hit
InterProiView 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
PANTHERiPTHR11716 PTHR11716, 1 hit
PfamiView protein in Pfam
PF00068 Phospholip_A2_1, 1 hit
PRINTSiPR00389 PHPHLIPASEA2
SMARTiView protein in SMART
SM00085 PA2c, 1 hit
SUPFAMiSSF48619 SSF48619, 1 hit
PROSITEiView protein in PROSITE
PS00119 PA2_ASP, 1 hit
PS00118 PA2_HIS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPA2GA_HUMAN
AccessioniPrimary (citable) accession number: P14555
Secondary accession number(s): A8K5I7
, Q6DN24, Q6IBD9, Q9UCD2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: April 1, 1990
Last modified: November 7, 2018
This is version 208 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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