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Protein

Phospholipase A2, membrane associated

Gene

PLA2G2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi47 – 471Calcium; via carbonyl oxygen
Metal bindingi49 – 491Calcium; via carbonyl oxygen
Metal bindingi51 – 511Calcium; via carbonyl oxygen
Active sitei67 – 671By similarity
Metal bindingi68 – 681Calcium
Sitei94 – 941Important for integrin binding1 Publication
Active sitei111 – 1111By similarity
Sitei120 – 1201Important for integrin binding1 Publication

GO - Molecular functioni

  • calcium-dependent phospholipase A2 activity Source: UniProtKB
  • calcium ion binding Source: InterPro
  • phospholipase A2 activity Source: BHF-UCL
  • phospholipid binding Source: BHF-UCL

GO - Biological processi

  • defense response to Gram-positive bacterium Source: BHF-UCL
  • lipid catabolic process Source: UniProtKB-KW
  • low-density lipoprotein particle remodeling Source: BHF-UCL
  • phosphatidic acid biosynthetic process Source: Reactome
  • phosphatidic acid metabolic process Source: BHF-UCL
  • phosphatidylcholine acyl-chain remodeling Source: Reactome
  • phosphatidylethanolamine acyl-chain remodeling Source: Reactome
  • phosphatidylglycerol acyl-chain remodeling Source: Reactome
  • phosphatidylinositol acyl-chain remodeling Source: Reactome
  • phosphatidylserine acyl-chain remodeling Source: Reactome
  • phospholipid metabolic process Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: CACAO
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of macrophage derived foam cell differentiation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid degradation, Lipid metabolism

Keywords - Ligandi

Calcium, 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.

Chemistry

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

HGNCiHGNC:9031. PLA2G2A.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 491G → S: No effect on integrin binding; when associated with K-68. 1 Publication
Mutagenesisi62 – 621R → E: No effect on integrin binding. 1 Publication
Mutagenesisi67 – 671H → Q: Catalytically inactive but does not affect integrin binding. 2 Publications
Mutagenesisi68 – 681D → K: No effect on integrin binding; when associated with S-49. 1 Publication
Mutagenesisi73 – 731R → E: Slightly reduced integrin binding. 1 Publication
Mutagenesisi94 – 941R → E: Moderately reduced integrin binding. Greatly reduced integrin binding but no effect on catalytic activity; when associated with E-120. 2 Publications
Mutagenesisi120 – 1201R → E: Moderately reduced integrin binding. Greatly reduced integrin binding but no effect on catalytic activity; when associated with E-94. 2 Publications

Organism-specific databases

MalaCardsiPLA2G2A.
PharmGKBiPA270.

Chemistry

ChEMBLiCHEMBL3474.
DrugBankiDB00586. Diclofenac.
DB01381. Ginkgo biloba.
DB00328. Indomethacin.
DB02325. Isopropyl Alcohol.
DB04786. Suramin.
GuidetoPHARMACOLOGYi1417.

Polymorphism and mutation databases

BioMutaiPLA2G2A.
DMDMi129483.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 20205 PublicationsAdd
BLAST
Chaini21 – 144124Phospholipase A2, membrane associatedPRO_0000022750Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
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

PaxDbiP14555.
PeptideAtlasiP14555.
PRIDEiP14555.

PTM databases

iPTMnetiP14555.
PhosphoSiteiP14555.

Expressioni

Gene expression databases

BgeeiENSG00000188257.
CleanExiHS_PLA2G2A.
ExpressionAtlasiP14555. baseline and differential.
GenevisibleiP14555. HS.

Organism-specific databases

HPAiHPA015236.

Interactioni

Protein-protein interaction databases

BioGridi111337. 22 interactions.
IntActiP14555. 3 interactions.
MINTiMINT-1206447.
STRINGi9606.ENSP00000364252.

Chemistry

BindingDBiP14555.

Structurei

Secondary structure

1
144
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi22 – 3312Combined sources
Helixi37 – 404Combined sources
Turni41 – 433Combined sources
Turni45 – 473Combined sources
Beta strandi48 – 503Combined sources
Helixi59 – 7618Combined sources
Beta strandi81 – 833Combined sources
Beta strandi88 – 914Combined sources
Beta strandi94 – 974Combined sources
Helixi102 – 12019Combined sources
Helixi122 – 1243Combined sources
Helixi127 – 1293Combined sources
Helixi134 – 1363Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP14555.
SMRiP14555. Positions 21-144.
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.
OMAiKQDSCRS.
OrthoDBiEOG091G0UZ3.
PhylomeDBiP14555.
TreeFamiTF319283.

Family and domain databases

Gene3Di1.20.90.10. 1 hit.
InterProiIPR001211. PLipase_A2.
IPR033112. PLipase_A2_Asp_AS.
IPR016090. PLipase_A2_dom.
IPR033113. PLipase_A2_His_AS.
[Graphical view]
PANTHERiPTHR11716. PTHR11716. 1 hit.
PfamiPF00068. Phospholip_A2_1. 1 hit.
[Graphical view]
PRINTSiPR00389. PHPHLIPASEA2.
SMARTiSM00085. PA2c. 1 hit.
[Graphical view]
SUPFAMiSSF48619. SSF48619. 1 hit.
PROSITEiPS00119. PA2_ASP. 1 hit.
PS00118. PA2_HIS. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti12 – 121I → Y in AAT73043 (Ref. 4) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 191H → Y.1 Publication
Corresponds to variant rs11573162 [ dbSNP | Ensembl ].
VAR_018953

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. Translation: CAH74017.1.
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

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. Translation: CAH74017.1.
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
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[»]
ProteinModelPortaliP14555.
SMRiP14555. Positions 21-144.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111337. 22 interactions.
IntActiP14555. 3 interactions.
MINTiMINT-1206447.
STRINGi9606.ENSP00000364252.

Chemistry

BindingDBiP14555.
ChEMBLiCHEMBL3474.
DrugBankiDB00586. Diclofenac.
DB01381. Ginkgo biloba.
DB00328. Indomethacin.
DB02325. Isopropyl Alcohol.
DB04786. Suramin.
GuidetoPHARMACOLOGYi1417.
SwissLipidsiSLP:000000653.

PTM databases

iPTMnetiP14555.
PhosphoSiteiP14555.

Polymorphism and mutation databases

BioMutaiPLA2G2A.
DMDMi129483.

Proteomic databases

PaxDbiP14555.
PeptideAtlasiP14555.
PRIDEiP14555.

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.
GeneCardsiPLA2G2A.
HGNCiHGNC:9031. PLA2G2A.
HPAiHPA015236.
MalaCardsiPLA2G2A.
MIMi172411. gene.
neXtProtiNX_P14555.
PharmGKBiPA270.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4087. Eukaryota.
ENOG411283D. LUCA.
GeneTreeiENSGT00760000119160.
HOGENOMiHOG000231749.
HOVERGENiHBG008137.
InParanoidiP14555.
KOiK01047.
OMAiKQDSCRS.
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.

Miscellaneous databases

ChiTaRSiPLA2G2A. human.
EvolutionaryTraceiP14555.
GeneWikiiPLA2G2A.
GenomeRNAii5320.
PROiP14555.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188257.
CleanExiHS_PLA2G2A.
ExpressionAtlasiP14555. baseline and differential.
GenevisibleiP14555. HS.

Family and domain databases

Gene3Di1.20.90.10. 1 hit.
InterProiIPR001211. PLipase_A2.
IPR033112. PLipase_A2_Asp_AS.
IPR016090. PLipase_A2_dom.
IPR033113. PLipase_A2_His_AS.
[Graphical view]
PANTHERiPTHR11716. PTHR11716. 1 hit.
PfamiPF00068. Phospholip_A2_1. 1 hit.
[Graphical view]
PRINTSiPR00389. PHPHLIPASEA2.
SMARTiSM00085. PA2c. 1 hit.
[Graphical view]
SUPFAMiSSF48619. SSF48619. 1 hit.
PROSITEiPS00119. PA2_ASP. 1 hit.
PS00118. PA2_HIS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPA2GA_HUMAN
AccessioniPrimary (citable) accession number: P14555
Secondary accession number(s): A8K5I7
, Q6DN24, Q6IBD9, Q9UCD2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: April 1, 1990
Last modified: September 7, 2016
This is version 190 of the entry and version 2 of the sequence. [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

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

Keywords - Technical termi

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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.