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Protein

Cytosolic phospholipase A2 gamma

Gene

PLA2G4C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has a preference for arachidonic acid at the sn-2 position of phosphatidylcholine as compared with palmitic acid.1 Publication

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.

Enzyme regulationi

Not regulated by calcium.

Kineticsi

    1. Vmax=218 pmol/min/mg enzyme1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei82NucleophileBy similarity1
    Active sitei385Proton acceptorBy similarity1

    GO - Molecular functioni

    • calcium-independent phospholipase A2 activity Source: UniProtKB
    • lysophospholipase activity Source: Reactome
    • phosphatidylcholine 1-acylhydrolase activity Source: Reactome
    • phospholipase A2 activity Source: Reactome
    • phospholipid binding Source: UniProtKB

    GO - Biological processi

    • arachidonic acid metabolic process Source: UniProtKB
    • glycerophospholipid catabolic process Source: UniProtKB
    • inflammatory response Source: UniProtKB
    • intracellular signal transduction Source: UniProtKB
    • parturition Source: UniProtKB
    • phosphatidylcholine acyl-chain remodeling Source: Reactome
    • phosphatidylethanolamine acyl-chain remodeling Source: Reactome
    • phosphatidylinositol acyl-chain remodeling Source: Reactome
    • phospholipid metabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Lipid degradation, Lipid metabolism

    Enzyme and pathway databases

    BioCyciZFISH:HS02750-MONOMER.
    ReactomeiR-HSA-1482788. Acyl chain remodelling of PC.
    R-HSA-1482839. Acyl chain remodelling of PE.
    R-HSA-1482922. Acyl chain remodelling of PI.
    R-HSA-1483115. Hydrolysis of LPC.
    R-HSA-1483152. Hydrolysis of LPE.

    Chemistry databases

    SwissLipidsiSLP:000000888.
    SLP:000001081. [Q9UP65-1]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytosolic phospholipase A2 gamma (EC:3.1.1.4)
    Short name:
    cPLA2-gamma
    Alternative name(s):
    Phospholipase A2 group IVC
    Gene namesi
    Name:PLA2G4C
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:9037. PLA2G4C.

    Subcellular locationi

    • Membrane 1 Publication; Lipid-anchor 1 Publication

    GO - Cellular componenti

    • cell cortex Source: Ensembl
    • cytosol Source: UniProtKB
    • endoplasmic reticulum membrane Source: Reactome
    • membrane Source: UniProtKB
    • nuclear envelope Source: Ensembl
    • nucleoplasm Source: Ensembl
    Complete GO annotation...

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi54R → A: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi82S → A: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi385D → A: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi402R → A: Abolishes enzyme activity. 1 Publication1

    Organism-specific databases

    DisGeNETi8605.
    OpenTargetsiENSG00000105499.
    PharmGKBiPA33365.

    Chemistry databases

    ChEMBLiCHEMBL4834.

    Polymorphism and mutation databases

    BioMutaiPLA2G4C.
    DMDMi322510066.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000229951 – 538Cytosolic phospholipase A2 gammaAdd BLAST538
    PropeptideiPRO_0000022996539 – 541Removed in mature form3

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei337PhosphoserineCombined sources1
    Modified residuei538Cysteine methyl ester1 Publication1
    Lipidationi538S-farnesyl cysteine1 Publication1

    Keywords - PTMi

    Lipoprotein, Methylation, Phosphoprotein, Prenylation

    Proteomic databases

    PaxDbiQ9UP65.
    PeptideAtlasiQ9UP65.
    PRIDEiQ9UP65.

    PTM databases

    iPTMnetiQ9UP65.
    PhosphoSitePlusiQ9UP65.
    SwissPalmiQ9UP65.

    Expressioni

    Tissue specificityi

    Highly expressed in heart and skeletal muscle.2 Publications

    Gene expression databases

    BgeeiENSG00000105499.
    CleanExiHS_PLA2G4C.
    ExpressionAtlasiQ9UP65. baseline and differential.
    GenevisibleiQ9UP65. HS.

    Organism-specific databases

    HPAiHPA043083.

    Interactioni

    Protein-protein interaction databases

    BioGridi114165. 2 interactors.
    STRINGi9606.ENSP00000400036.

    Chemistry databases

    BindingDBiQ9UP65.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UP65.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini1 – 541PLA2cPROSITE-ProRule annotationAdd BLAST541

    Sequence similaritiesi

    Contains 1 PLA2c domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG1325. Eukaryota.
    ENOG410XR72. LUCA.
    GeneTreeiENSGT00550000074489.
    HOGENOMiHOG000059624.
    HOVERGENiHBG058910.
    InParanoidiQ9UP65.
    KOiK16342.
    OMAiLFNIDAC.
    OrthoDBiEOG091G04R7.
    PhylomeDBiQ9UP65.
    TreeFamiTF325228.

    Family and domain databases

    InterProiIPR016035. Acyl_Trfase/lysoPLipase.
    IPR002642. LysoPLipase_cat_dom.
    [Graphical view]
    PfamiPF01735. PLA2_B. 1 hit.
    [Graphical view]
    SMARTiSM00022. PLAc. 1 hit.
    [Graphical view]
    SUPFAMiSSF52151. SSF52151. 1 hit.
    PROSITEiPS51210. PLA2C. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9UP65-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MGSSEVSIIP GLQKEEKAAV ERRRLHVLKA LKKLRIEADE APVVAVLGSG
    60 70 80 90 100
    GGLRAHIACL GVLSEMKEQG LLDAVTYLAG VSGSTWAISS LYTNDGDMEA
    110 120 130 140 150
    LEADLKHRFT RQEWDLAKSL QKTIQAARSE NYSLTDFWAY MVISKQTREL
    160 170 180 190 200
    PESHLSNMKK PVEEGTLPYP IFAAIDNDLQ PSWQEARAPE TWFEFTPHHA
    210 220 230 240 250
    GFSALGAFVS ITHFGSKFKK GRLVRTHPER DLTFLRGLWG SALGNTEVIR
    260 270 280 290 300
    EYIFDQLRNL TLKGLWRRAV ANAKSIGHLI FARLLRLQES SQGEHPPPED
    310 320 330 340 350
    EGGEPEHTWL TEMLENWTRT SLEKQEQPHE DPERKGSLSN LMDFVKKTGI
    360 370 380 390 400
    CASKWEWGTT HNFLYKHGGI RDKIMSSRKH LHLVDAGLAI NTPFPLVLPP
    410 420 430 440 450
    TREVHLILSF DFSAGDPFET IRATTDYCRR HKIPFPQVEE AELDLWSKAP
    460 470 480 490 500
    ASCYILKGET GPVVMHFPLF NIDACGGDIE AWSDTYDTFK LADTYTLDVV
    510 520 530 540
    VLLLALAKKN VRENKKKILR ELMNVAGLYY PKDSARSCCL A
    Length:541
    Mass (Da):60,939
    Last modified:February 8, 2011 - v2
    Checksum:iA114B2A614EA4632
    GO
    Isoform 2 (identifier: Q9UP65-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         528-541: Missing.

    Show »
    Length:527
    Mass (Da):59,367
    Checksum:i4F4C4884DE7EAD3A
    GO
    Isoform 3 (identifier: Q9UP65-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-13: MGSSEVSIIPGLQ → MRTRPRPRLRRTENFLTAVHHGK

    Show »
    Length:551
    Mass (Da):62,451
    Checksum:iD9A68B760776F943
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti24R → G in BAG58352 (PubMed:14702039).Curated1
    Sequence conflicti465M → I in AAC32823 (PubMed:9705332).Curated1
    Sequence conflicti480E → G in CAG33097 (Ref. 5) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_01876121E → K.1 PublicationCorresponds to variant rs11564522dbSNPEnsembl.1
    Natural variantiVAR_01842038A → P.1 PublicationCorresponds to variant rs2307279dbSNPEnsembl.1
    Natural variantiVAR_018762127A → V.1 PublicationCorresponds to variant rs11564532dbSNPEnsembl.1
    Natural variantiVAR_018763142V → F.1 PublicationCorresponds to variant rs11564534dbSNPEnsembl.1
    Natural variantiVAR_018421143I → V.2 PublicationsCorresponds to variant rs2303744dbSNPEnsembl.1
    Natural variantiVAR_018764148R → G.1 PublicationCorresponds to variant rs2307282dbSNPEnsembl.1
    Natural variantiVAR_018765151P → L.1 PublicationCorresponds to variant rs11564538dbSNPEnsembl.1
    Natural variantiVAR_018422203S → P.4 PublicationsCorresponds to variant rs156631dbSNPEnsembl.1
    Natural variantiVAR_018766226T → S.1 PublicationCorresponds to variant rs11564541dbSNPEnsembl.1
    Natural variantiVAR_018767360T → P.1 PublicationCorresponds to variant rs11564620dbSNPEnsembl.1
    Natural variantiVAR_018768411D → N.1 PublicationCorresponds to variant rs11564638dbSNPEnsembl.1
    Natural variantiVAR_018423430R → C.1 PublicationCorresponds to variant rs191276960dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0458491 – 13MGSSE…IPGLQ → MRTRPRPRLRRTENFLTAVH HGK in isoform 3. 1 PublicationAdd BLAST13
    Alternative sequenceiVSP_045850528 – 541Missing in isoform 2. CuratedAdd BLAST14

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF058921 mRNA. Translation: AAC32823.1.
    AF065214 mRNA. Translation: AAC78835.1.
    AY485310 Genomic DNA. Translation: AAR25453.1.
    AK295400 mRNA. Translation: BAG58352.1.
    AK314524 mRNA. Translation: BAG37118.1.
    CR456816 mRNA. Translation: CAG33097.1.
    AC010458 Genomic DNA. No translation available.
    AC011466 Genomic DNA. No translation available.
    CH471177 Genomic DNA. Translation: EAW52314.1.
    BC063416 mRNA. Translation: AAH63416.1.
    AB105807 Genomic DNA. Translation: BAC87745.1.
    AL050193 mRNA. Translation: CAB43312.3.
    CCDSiCCDS12710.1. [Q9UP65-1]
    CCDS54286.1. [Q9UP65-2]
    CCDS59403.1. [Q9UP65-3]
    PIRiT13162.
    RefSeqiNP_001152794.1. NM_001159322.1. [Q9UP65-3]
    NP_001152795.1. NM_001159323.1. [Q9UP65-2]
    NP_003697.2. NM_003706.2. [Q9UP65-1]
    UniGeneiHs.631562.

    Genome annotation databases

    EnsembliENST00000354276; ENSP00000346228; ENSG00000105499. [Q9UP65-2]
    ENST00000599111; ENSP00000472546; ENSG00000105499. [Q9UP65-3]
    ENST00000599921; ENSP00000469473; ENSG00000105499. [Q9UP65-1]
    GeneIDi8605.
    KEGGihsa:8605.
    UCSCiuc002phx.4. human. [Q9UP65-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF058921 mRNA. Translation: AAC32823.1.
    AF065214 mRNA. Translation: AAC78835.1.
    AY485310 Genomic DNA. Translation: AAR25453.1.
    AK295400 mRNA. Translation: BAG58352.1.
    AK314524 mRNA. Translation: BAG37118.1.
    CR456816 mRNA. Translation: CAG33097.1.
    AC010458 Genomic DNA. No translation available.
    AC011466 Genomic DNA. No translation available.
    CH471177 Genomic DNA. Translation: EAW52314.1.
    BC063416 mRNA. Translation: AAH63416.1.
    AB105807 Genomic DNA. Translation: BAC87745.1.
    AL050193 mRNA. Translation: CAB43312.3.
    CCDSiCCDS12710.1. [Q9UP65-1]
    CCDS54286.1. [Q9UP65-2]
    CCDS59403.1. [Q9UP65-3]
    PIRiT13162.
    RefSeqiNP_001152794.1. NM_001159322.1. [Q9UP65-3]
    NP_001152795.1. NM_001159323.1. [Q9UP65-2]
    NP_003697.2. NM_003706.2. [Q9UP65-1]
    UniGeneiHs.631562.

    3D structure databases

    ProteinModelPortaliQ9UP65.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114165. 2 interactors.
    STRINGi9606.ENSP00000400036.

    Chemistry databases

    BindingDBiQ9UP65.
    ChEMBLiCHEMBL4834.
    SwissLipidsiSLP:000000888.
    SLP:000001081. [Q9UP65-1]

    PTM databases

    iPTMnetiQ9UP65.
    PhosphoSitePlusiQ9UP65.
    SwissPalmiQ9UP65.

    Polymorphism and mutation databases

    BioMutaiPLA2G4C.
    DMDMi322510066.

    Proteomic databases

    PaxDbiQ9UP65.
    PeptideAtlasiQ9UP65.
    PRIDEiQ9UP65.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000354276; ENSP00000346228; ENSG00000105499. [Q9UP65-2]
    ENST00000599111; ENSP00000472546; ENSG00000105499. [Q9UP65-3]
    ENST00000599921; ENSP00000469473; ENSG00000105499. [Q9UP65-1]
    GeneIDi8605.
    KEGGihsa:8605.
    UCSCiuc002phx.4. human. [Q9UP65-1]

    Organism-specific databases

    CTDi8605.
    DisGeNETi8605.
    GeneCardsiPLA2G4C.
    HGNCiHGNC:9037. PLA2G4C.
    HPAiHPA043083.
    MIMi603602. gene.
    neXtProtiNX_Q9UP65.
    OpenTargetsiENSG00000105499.
    PharmGKBiPA33365.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1325. Eukaryota.
    ENOG410XR72. LUCA.
    GeneTreeiENSGT00550000074489.
    HOGENOMiHOG000059624.
    HOVERGENiHBG058910.
    InParanoidiQ9UP65.
    KOiK16342.
    OMAiLFNIDAC.
    OrthoDBiEOG091G04R7.
    PhylomeDBiQ9UP65.
    TreeFamiTF325228.

    Enzyme and pathway databases

    BioCyciZFISH:HS02750-MONOMER.
    ReactomeiR-HSA-1482788. Acyl chain remodelling of PC.
    R-HSA-1482839. Acyl chain remodelling of PE.
    R-HSA-1482922. Acyl chain remodelling of PI.
    R-HSA-1483115. Hydrolysis of LPC.
    R-HSA-1483152. Hydrolysis of LPE.

    Miscellaneous databases

    GeneWikiiPLA2G4C.
    GenomeRNAii8605.
    PROiQ9UP65.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000105499.
    CleanExiHS_PLA2G4C.
    ExpressionAtlasiQ9UP65. baseline and differential.
    GenevisibleiQ9UP65. HS.

    Family and domain databases

    InterProiIPR016035. Acyl_Trfase/lysoPLipase.
    IPR002642. LysoPLipase_cat_dom.
    [Graphical view]
    PfamiPF01735. PLA2_B. 1 hit.
    [Graphical view]
    SMARTiSM00022. PLAc. 1 hit.
    [Graphical view]
    SUPFAMiSSF52151. SSF52151. 1 hit.
    PROSITEiPS51210. PLA2C. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPA24C_HUMAN
    AccessioniPrimary (citable) accession number: Q9UP65
    Secondary accession number(s): B2RB71
    , B4DI40, O75457, Q6IBI8, Q9UG68
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 10, 2004
    Last sequence update: February 8, 2011
    Last modified: November 2, 2016
    This is version 130 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: 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. 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.