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Protein

Cytosolic phospholipase A2

Gene

PLA2G4A

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

Functioni

Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
2-lysophosphatidylcholine + H2O = glycerophosphocholine + a carboxylate.

Enzyme regulationi

Stimulated by agonists such as ATP, EGF, thrombin and bradykinin as well as by cytosolic Ca2+.

Kineticsi

    1. Vmax=2.7 µmol/min/mg enzyme for the phospholipase A2 reaction1 Publication
    2. Vmax=4.6 µmol/min/mg enzyme for the lysophosphatase reaction1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi40Calcium 11
    Metal bindingi40Calcium 21
    Metal bindingi41Calcium 1; via carbonyl oxygen1
    Metal bindingi43Calcium 11
    Metal bindingi43Calcium 21
    Metal bindingi65Calcium 11
    Metal bindingi93Calcium 21
    Metal bindingi94Calcium 2; via carbonyl oxygen1
    Metal bindingi95Calcium 21
    Active sitei228Nucleophile4 Publications1
    Active sitei549Proton acceptor2 Publications1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

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

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04039-MONOMER
    BRENDAi3.1.1.4 2681
    ReactomeiR-HSA-111995 phospho-PLA2 pathway
    R-HSA-1482788 Acyl chain remodelling of PC
    R-HSA-1482798 Acyl chain remodeling of CL
    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-1483115 Hydrolysis of LPC
    R-HSA-1483166 Synthesis of PA
    R-HSA-2142753 Arachidonic acid metabolism
    R-HSA-418592 ADP signalling through P2Y purinoceptor 1
    R-HSA-432142 Platelet sensitization by LDL
    R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic
    SIGNORiP47712

    Chemistry databases

    SwissLipidsiSLP:000000565

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytosolic phospholipase A2
    Short name:
    cPLA2
    Alternative name(s):
    Phospholipase A2 group IVA
    Including the following 2 domains:
    Phospholipase A2 (EC:3.1.1.4)
    Alternative name(s):
    Phosphatidylcholine 2-acylhydrolase
    Lysophospholipase (EC:3.1.1.5)
    Gene namesi
    Name:PLA2G4A
    Synonyms:CPLA2, PLA2G4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000116711.9
    HGNCiHGNC:9035 PLA2G4A
    MIMi600522 gene
    neXtProtiNX_P47712

    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

    Cytoplasm, Cytoplasmic vesicle

    Pathology & Biotechi

    Involvement in diseasei

    PLA2G4A mutations resulting in phospholipase A2 deficiency have been found in a patient affected by recurrent episodes of multiple complicated ulcers of the small intestine, not due to cyclooxygenase inhibitors use. Disease features also include platelet dysfunction, and globally decreased eicosanoid synthesis (PubMed:18451993).1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi139C → A: No effect on phospholipase activity; when associated with A-141 and A-151. 1 Publication1
    Mutagenesisi141C → A: No effect on phospholipase activity; when associated with A-139 and A-151. 1 Publication1
    Mutagenesisi151C → A: No effect on phospholipase activity; when associated with A-139 and A-141. 1 Publication1
    Mutagenesisi195S → A: 5-fold reduced phospholipase and lysophosphatase activities. 100-fold reduced phospholipase and lysophosphatase activities; when associated with A-577. 1 Publication1
    Mutagenesisi200R → A or H: Abolishes phospholipase activity. 1 Publication1
    Mutagenesisi200R → K: Reduces phospholipase activity 200-fold. 1 Publication1
    Mutagenesisi215S → A: No effect on phospholipase or lysophosphatase activity. 1 Publication1
    Mutagenesisi220C → A: No effect on phospholipase activity. 1 Publication1
    Mutagenesisi228S → A, C or T: Abolishes both phospholipase and lysophosphatase activities. 3 Publications1
    Mutagenesisi324C → A: No effect on phospholipase activity; when associated with A-331. 1 Publication1
    Mutagenesisi331C → A: No effect on phospholipase activity; when associated with A-324. 1 Publication1
    Mutagenesisi505S → A: Decreases agonist-stimulated release of arachidonic acid. 1 Publication1
    Mutagenesisi549D → A: Abolishes phospholipiase activity. 1 Publication1
    Mutagenesisi549D → E: Reduces phospholipiase activity 2000-fold. 1 Publication1
    Mutagenesisi549D → N: Reduces phospholipiase activity 300-fold. 1 Publication1
    Mutagenesisi577S → A: 7-fold reduced phospholipase and lysophosphatase activities. 100-fold reduced phospholipase and lysophosphatase activities; when associated with A-195. 1 Publication1
    Mutagenesisi620C → A: No effect on phospholipase activity; when associated with A-634. 1 Publication1
    Mutagenesisi634C → A: No effect on phospholipase activity; when associated with A-620. 1 Publication1
    Mutagenesisi726C → A: No effect on phospholipase activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi5321
    MalaCardsiPLA2G4A
    OpenTargetsiENSG00000116711
    PharmGKBiPA271

    Chemistry databases

    ChEMBLiCHEMBL3816
    DrugBankiDB00041 Aldesleukin
    DB00411 Carbachol
    DB00578 Carbenicillin
    DB05029 Duramycin
    DB00445 Epirubicin
    DB04827 Ethyl carbamate
    DB00591 Fluocinolone Acetonide
    DB00588 Fluticasone Propionate
    DB04552 Niflumic Acid
    DB01083 Orlistat
    DB01103 Quinacrine
    DB00086 Streptokinase
    DB04786 Suramin
    GuidetoPHARMACOLOGYi1424

    Polymorphism and mutation databases

    BioMutaiPLA2G4A
    DMDMi317373312

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001872621 – 749Cytosolic phospholipase A2Add BLAST749

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2PhosphoserineCombined sources1
    Modified residuei268PhosphothreonineCombined sources1
    Modified residuei434PhosphoserineBy similarity1
    Modified residuei435PhosphoserineCombined sources1
    Modified residuei437PhosphoserineCombined sources1
    Modified residuei505Phosphoserine; by MAPK2 Publications1
    Modified residuei515PhosphoserineBy similarity1
    Cross-linki541Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
    Cross-linki606Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
    Modified residuei727PhosphoserineCombined sources1 Publication1
    Modified residuei729PhosphoserineCombined sources1

    Post-translational modificationi

    Activated by phosphorylation at both Ser-505 and Ser-727.2 Publications

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    EPDiP47712
    MaxQBiP47712
    PaxDbiP47712
    PeptideAtlasiP47712
    PRIDEiP47712
    ProteomicsDBi55788

    PTM databases

    iPTMnetiP47712
    PhosphoSitePlusiP47712

    Miscellaneous databases

    PMAP-CutDBiP47712

    Expressioni

    Tissue specificityi

    Expressed in various tissues such as macrophages, platelets, neutrophils, fibroblasts and lung endothelium.

    Gene expression databases

    BgeeiENSG00000116711
    CleanExiHS_PLA2G4A
    GenevisibleiP47712 HS

    Organism-specific databases

    HPAiCAB010050
    HPA050062
    HPA054206

    Interactioni

    Subunit structurei

    Interacts with KAT5.4 Publications

    Protein-protein interaction databases

    BioGridi111338, 34 interactors
    DIPiDIP-40991N
    IntActiP47712, 10 interactors
    MINTiP47712
    STRINGi9606.ENSP00000356436

    Chemistry databases

    BindingDBiP47712

    Structurei

    Secondary structure

    1749
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi18 – 29Combined sources12
    Helixi34 – 39Combined sources6
    Beta strandi44 – 49Combined sources6
    Beta strandi51 – 54Combined sources4
    Beta strandi57 – 60Combined sources4
    Beta strandi70 – 79Combined sources10
    Beta strandi86 – 93Combined sources8
    Beta strandi96 – 98Combined sources3
    Beta strandi100 – 108Combined sources9
    Helixi109 – 111Combined sources3
    Beta strandi117 – 124Combined sources8
    Turni125 – 127Combined sources3
    Beta strandi128 – 137Combined sources10
    Beta strandi143 – 146Combined sources4
    Helixi152 – 177Combined sources26
    Helixi179 – 181Combined sources3
    Beta strandi190 – 194Combined sources5
    Helixi198 – 214Combined sources17
    Helixi218 – 220Combined sources3
    Beta strandi221 – 226Combined sources6
    Helixi228 – 239Combined sources12
    Turni241 – 245Combined sources5
    Helixi248 – 260Combined sources13
    Helixi263 – 266Combined sources4
    Helixi269 – 284Combined sources16
    Helixi291 – 304Combined sources14
    Helixi305 – 307Combined sources3
    Helixi313 – 318Combined sources6
    Turni319 – 321Combined sources3
    Beta strandi326 – 333Combined sources8
    Helixi341 – 343Combined sources3
    Beta strandi344 – 349Combined sources6
    Beta strandi354 – 356Combined sources3
    Turni357 – 360Combined sources4
    Beta strandi361 – 363Combined sources3
    Helixi365 – 367Combined sources3
    Beta strandi370 – 373Combined sources4
    Beta strandi376 – 379Combined sources4
    Helixi386 – 393Combined sources8
    Helixi396 – 399Combined sources4
    Helixi401 – 404Combined sources4
    Helixi417 – 423Combined sources7
    Helixi426 – 429Combined sources4
    Helixi463 – 476Combined sources14
    Beta strandi488 – 490Combined sources3
    Turni492 – 495Combined sources4
    Beta strandi543 – 548Combined sources6
    Helixi550 – 552Combined sources3
    Helixi558 – 561Combined sources4
    Helixi564 – 566Combined sources3
    Beta strandi570 – 575Combined sources6
    Helixi588 – 599Combined sources12
    Helixi611 – 615Combined sources5
    Beta strandi619 – 623Combined sources5
    Beta strandi636 – 641Combined sources6
    Helixi646 – 648Combined sources3
    Beta strandi650 – 652Combined sources3
    Helixi660 – 666Combined sources7
    Beta strandi670 – 672Combined sources3
    Helixi687 – 702Combined sources16
    Helixi705 – 718Combined sources14

    3D structure databases

    ProteinModelPortaliP47712
    SMRiP47712
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP47712

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini5 – 106C2PROSITE-ProRule annotationAdd BLAST102
    Domaini140 – 740PLA2cPROSITE-ProRule annotationAdd BLAST601

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 178Phospholipid bindingCuratedAdd BLAST178

    Domaini

    The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca2+.2 Publications

    Phylogenomic databases

    eggNOGiKOG1012 Eukaryota
    KOG1325 Eukaryota
    ENOG410XR72 LUCA
    GeneTreeiENSGT00550000074489
    HOGENOMiHOG000115420
    HOVERGENiHBG053479
    InParanoidiP47712
    KOiK16342
    OMAiRFSMALC
    OrthoDBiEOG091G0276
    PhylomeDBiP47712
    TreeFamiTF325228

    Family and domain databases

    Gene3Di2.60.40.150, 1 hit
    InterProiView protein in InterPro
    IPR016035 Acyl_Trfase/lysoPLipase
    IPR000008 C2_dom
    IPR035892 C2_domain_sf
    IPR002642 LysoPLipase_cat_dom
    PfamiView protein in Pfam
    PF00168 C2, 1 hit
    PF01735 PLA2_B, 1 hit
    SMARTiView protein in SMART
    SM00239 C2, 1 hit
    SM00022 PLAc, 1 hit
    SUPFAMiSSF52151 SSF52151, 1 hit
    PROSITEiView protein in PROSITE
    PS50004 C2, 1 hit
    PS51210 PLA2C, 1 hit

    Sequencei

    Sequence statusi: Complete.

    P47712-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSFIDPYQHI IVEHQYSHKF TVVVLRATKV TKGAFGDMLD TPDPYVELFI
    60 70 80 90 100
    STTPDSRKRT RHFNNDINPV WNETFEFILD PNQENVLEIT LMDANYVMDE
    110 120 130 140 150
    TLGTATFTVS SMKVGEKKEV PFIFNQVTEM VLEMSLEVCS CPDLRFSMAL
    160 170 180 190 200
    CDQEKTFRQQ RKEHIRESMK KLLGPKNSEG LHSARDVPVV AILGSGGGFR
    210 220 230 240 250
    AMVGFSGVMK ALYESGILDC ATYVAGLSGS TWYMSTLYSH PDFPEKGPEE
    260 270 280 290 300
    INEELMKNVS HNPLLLLTPQ KVKRYVESLW KKKSSGQPVT FTDIFGMLIG
    310 320 330 340 350
    ETLIHNRMNT TLSSLKEKVN TAQCPLPLFT CLHVKPDVSE LMFADWVEFS
    360 370 380 390 400
    PYEIGMAKYG TFMAPDLFGS KFFMGTVVKK YEENPLHFLM GVWGSAFSIL
    410 420 430 440 450
    FNRVLGVSGS QSRGSTMEEE LENITTKHIV SNDSSDSDDE SHEPKGTENE
    460 470 480 490 500
    DAGSDYQSDN QASWIHRMIM ALVSDSALFN TREGRAGKVH NFMLGLNLNT
    510 520 530 540 550
    SYPLSPLSDF ATQDSFDDDE LDAAVADPDE FERIYEPLDV KSKKIHVVDS
    560 570 580 590 600
    GLTFNLPYPL ILRPQRGVDL IISFDFSARP SDSSPPFKEL LLAEKWAKMN
    610 620 630 640 650
    KLPFPKIDPY VFDREGLKEC YVFKPKNPDM EKDCPTIIHF VLANINFRKY
    660 670 680 690 700
    RAPGVPRETE EEKEIADFDI FDDPESPFST FNFQYPNQAF KRLHDLMHFN
    710 720 730 740
    TLNNIDVIKE AMVESIEYRR QNPSRCSVSL SNVEARRFFN KEFLSKPKA
    Length:749
    Mass (Da):85,239
    Last modified:January 11, 2011 - v2
    Checksum:iEE71CA0EBE617856
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_029276103G → R. Corresponds to variant dbSNP:rs28395828Ensembl.1
    Natural variantiVAR_070778111S → P Probable disease-associated mutation found in a compound heterozygote affected by phospholipase A2 deficiency also carrying H-485. 1 PublicationCorresponds to variant dbSNP:rs121434634EnsemblClinVar.1
    Natural variantiVAR_018760224V → I1 PublicationCorresponds to variant dbSNP:rs12720588Ensembl.1
    Natural variantiVAR_035826442H → Q in a breast cancer sample; somatic mutation. 1 Publication1
    Natural variantiVAR_070779485R → H Probable disease-associated mutation found in a compound heterozygote affected by phospholipase A2 deficiency also carrying P-111. 1 PublicationCorresponds to variant dbSNP:rs121434635EnsemblClinVar.1
    Natural variantiVAR_062128637I → V. Corresponds to variant dbSNP:rs28395831Ensembl.1
    Natural variantiVAR_018424651R → K5 PublicationsCorresponds to variant dbSNP:rs2307198Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M72393 mRNA Translation: AAB00789.1
    M68874 mRNA Translation: AAA60105.1
    AY552098 Genomic DNA Translation: AAS45712.1
    AL022147 Genomic DNA No translation available.
    AL049797 Genomic DNA No translation available.
    BC114340 mRNA Translation: AAI14341.1
    CCDSiCCDS1372.1
    PIRiA39329
    RefSeqiNP_001298122.1, NM_001311193.1
    NP_077734.1, NM_024420.2
    XP_011507944.1, XM_011509642.2
    UniGeneiHs.497200

    Genome annotation databases

    EnsembliENST00000367466; ENSP00000356436; ENSG00000116711
    GeneIDi5321
    KEGGihsa:5321
    UCSCiuc001gsc.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiPA24A_HUMAN
    AccessioniPrimary (citable) accession number: P47712
    Secondary accession number(s): B1AKG4, Q29R80
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: January 11, 2011
    Last modified: July 18, 2018
    This is version 192 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. 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

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