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Protein

Cytosolic phospholipase A2 beta

Gene

PLA2G4B

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

Functioni

Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position with a preference for arachidonoyl phospholipids. Has a much weaker activity than PLA2G4A. Isoform 3 has calcium-dependent activity against palmitoyl-arachidonyl-phosphatidylethanolamine and low level lysophospholipase activity but no activity against phosphatidylcholine. Isoform 5 does have activity against phosphatidylcholine.3 Publications

Caution

Most tissues also express read-through transcripts from this gene into the upstream gene (JMJD7), some of which may encode fusion proteins.Curated

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.3 Publications

Activity regulationi

Stimulated by cytosolic Ca2+.2 Publications

Kineticsi

    1. Vmax=7.9 pmol/min/mg enzyme (isoform 5)1 Publication
    2. Vmax=3.6 pmol/min/µg enzyme with cAMP as substrate (isoform 4)1 Publication
    3. Vmax=140 nmol/min/µg enzyme with 1-[14C]16:0-2-lyso-PC as substrate (isoform 5)1 Publication
    4. Vmax=1.6 nmol/min/µg enzyme with 1-[14C]16:0-2-lyso-PC as substrate (isoform 3)1 Publication
    5. Vmax=2.1 nmol/min/µg enzyme with 1-16:0-2-[14C]20:4-PC as substrate (isoform 5)1 Publication
    6. Vmax=0.6 nmol/min/µg enzyme with 1-16:0-2-[14C]20:4-PE as substrate (isoform 5)1 Publication
    7. Vmax=0.8 nmol/min/µg enzyme with 1-16:0-2-[14C]20:4-PE as substrate (isoform 3)1 Publication
    8. Vmax=0.3 nmol/min/µg enzyme with 1-16:0-2-[14C]18:2-PE as substrate (isoform 3)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei335NucleophileBy similarity1
    Active sitei615Proton acceptorBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

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

    Enzyme and pathway databases

    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-1482925 Acyl chain remodelling of PG
    R-HSA-1483115 Hydrolysis of LPC
    R-HSA-1483166 Synthesis of PA
    R-HSA-381038 XBP1(S) activates chaperone genes

    Chemistry databases

    SwissLipidsiSLP:000000616 [P0C869-8]
    SLP:000000617 [P0C869-6]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytosolic phospholipase A2 beta (EC:3.1.1.4)
    Short name:
    cPLA2-beta
    Alternative name(s):
    Phospholipase A2 group IVB
    Gene namesi
    Name:PLA2G4B
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000168970.21
    HostDB:ENSG00000243708.9
    HGNCiHGNC:9036 PLA2G4B
    MIMi606088 gene
    neXtProtiNX_P0C869

    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, Endosome, Membrane, Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi335S → A: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi417H → A: No effect. 1 Publication1
    Mutagenesisi615D → A: Abolishes enzyme activity. 1 Publication1
    Mutagenesisi632R → A: Abolishes enzyme activity. 1 Publication1

    Organism-specific databases

    DisGeNETi100137049
    8681
    OpenTargetsiENSG00000168970
    ENSG00000243708
    PharmGKBiPA165479070

    Chemistry databases

    ChEMBLiCHEMBL4136

    Polymorphism and mutation databases

    BioMutaiPLA2G4B
    DMDMi300669659

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002470211 – 781Cytosolic phospholipase A2 betaAdd BLAST781

    Proteomic databases

    EPDiP0C869
    MaxQBiP0C869
    PaxDbiP0C869
    PeptideAtlasiP0C869
    PRIDEiP0C869
    ProteomicsDBi52403
    52404 [P0C869-4]
    52405 [P0C869-6]
    52406 [P0C869-7]
    52407 [P0C869-8]

    PTM databases

    iPTMnetiP0C869
    PhosphoSitePlusiP0C869

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed at higher level in brain, heart, liver, cerebellum and pancreas. Isoform 3 is widely expressed.3 Publications

    Gene expression databases

    BgeeiENSG00000168970 Expressed in 86 organ(s), highest expression level in right hemisphere of cerebellum
    ExpressionAtlasiP0C869 baseline and differential
    GenevisibleiP0C869 HS

    Organism-specific databases

    HPAiHPA005726

    Interactioni

    Protein-protein interaction databases

    BioGridi114229, 2 interactors
    936685, 4 interactors
    IntActiP0C869, 3 interactors
    STRINGi9606.ENSP00000396045

    Chemistry databases

    BindingDBiP0C869

    Structurei

    3D structure databases

    ProteinModelPortaliP0C869
    SMRiP0C869
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini1 – 97C2PROSITE-ProRule annotationAdd BLAST97
    Domaini246 – 781PLA2cPROSITE-ProRule annotationAdd BLAST536

    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+ (By similarity).By similarity

    Phylogenomic databases

    eggNOGiKOG1028 Eukaryota
    KOG1325 Eukaryota
    ENOG410XR72 LUCA
    GeneTreeiENSGT00550000074489
    HOVERGENiHBG080412
    InParanoidiP0C869
    KOiK16342
    OMAiFRFRIHS
    OrthoDBiEOG091G011T
    PhylomeDBiP0C869
    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

    Sequences (5+)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 5 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

    Isoform 1 (identifier: P0C869-1) [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
    MAVAEVSRTC LLTVRVLQAH RLPSKDLVTP SDCYVTLWLP TACSHRLQTR
    60 70 80 90 100
    TVKNSSSPVW NQSFHFRIHR QLKNVMELKV FDQDLVTGDD PVLSVLFDAG
    110 120 130 140 150
    TLRAGEFRRE SFSLSPQGEG RLEVEFRLQS LADRGEWLVS NGVLVARELS
    160 170 180 190 200
    CLHVQLEETG DQKSSEHRVQ LVVPGSCEGP QEASVGTGTF RFHCPACWEQ
    210 220 230 240 250
    ELSIRLQDAP EEQLKAPLSA LPSGQVVRLV FPTSQEPLMR VELKKEAGLR
    260 270 280 290 300
    ELAVRLGFGP CAEEQAFLSR RKQVVAAALR QALQLDGDLQ EDEIPVVAIM
    310 320 330 340 350
    ATGGGIRAMT SLYGQLAGLK ELGLLDCVSY ITGASGSTWA LANLYEDPEW
    360 370 380 390 400
    SQKDLAGPTE LLKTQVTKNK LGVLAPSQLQ RYRQELAERA RLGYPSCFTN
    410 420 430 440 450
    LWALINEALL HDEPHDHKLS DQREALSHGQ NPLPIYCALN TKGQSLTTFE
    460 470 480 490 500
    FGEWCEFSPY EVGFPKYGAF IPSELFGSEF FMGQLMKRLP ESRICFLEGI
    510 520 530 540 550
    WSNLYAANLQ DSLYWASEPS QFWDRWVRNQ ANLDKEQVPL LKIEEPPSTA
    560 570 580 590 600
    GRIAEFFTDL LTWRPLAQAT HNFLRGLHFH KDYFQHPHFS TWKATTLDGL
    610 620 630 640 650
    PNQLTPSEPH LCLLDVGYLI NTSCLPLLQP TRDVDLILSL DYNLHGAFQQ
    660 670 680 690 700
    LQLLGRFCQE QGIPFPPISP SPEEQLQPRE CHTFSDPTCP GAPAVLHFPL
    710 720 730 740 750
    VSDSFREYSA PGVRRTPEEA AAGEVNLSSS DSPYHYTKVT YSQEDVDKLL
    760 770 780
    HLTHYNVCNN QEQLLEALRQ AVQRRRQRRP H
    Length:781
    Mass (Da):87,978
    Last modified:July 13, 2010 - v2
    Checksum:i4C5C6861E7BAB1B8
    GO
    Isoform 2 (identifier: P0C869-7) [UniParc]FASTAAdd to basket
    Also known as: beta2

    The sequence of this isoform differs from the canonical sequence as follows:
         1-3: MAV → MAEAALEAVR...KVVDEEAMEK
         650-662: QLQLLGRFCQEQG → GSGGHPRRRQLGR
         663-781: Missing.

    Note: Based on a naturally occurring readthrough transcript which produces a JMJD7-PLA2G4B fusion protein.
    Show »
    Length:893
    Mass (Da):100,516
    Checksum:i0A7C3BE752C48F55
    GO
    Isoform 3 (identifier: P0C869-8) [UniParc]FASTAAdd to basket
    Also known as: beta3

    The sequence of this isoform differs from the canonical sequence as follows:
         1-3: MAV → MAEAALEAVR...KVVDEEAMEK
         641-765: Missing.

    Note: Based on a naturally occurring readthrough transcript which produces a JMJD7-PLA2G4B fusion protein.
    Show »
    Length:887
    Mass (Da):100,094
    Checksum:i4C5CC6D084F2DF99
    GO
    Isoform 4 (identifier: P0C869-4) [UniParc] [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-299: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:482
    Mass (Da):54,679
    Checksum:iEB8FC2F2EB2AE258
    GO
    Isoform 5 (identifier: P0C869-6) [UniParc]FASTAAdd to basket
    Also known as: Beta1

    The sequence of this isoform differs from the canonical sequence as follows:
         1-3: MAV → MAEAALEAVR...KVVDEEAMEK

    Note: Based on a naturally occurring readthrough transcript which produces a JMJD7-PLA2G4B fusion protein.
    Show »
    Length:1,012
    Mass (Da):114,121
    Checksum:i989EDB4AD3CF19DD
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H3BSX5H3BSX5_HUMAN
    Cytosolic phospholipase A2 beta
    PLA2G4B
    30Annotation score:

    Sequence cautioni

    The sequence BAD92387 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti138L → F in AAD32135 (PubMed:10358058).Curated1
    Sequence conflicti162Q → P in ABF69195 (PubMed:16617059).Curated1
    Sequence conflicti162Q → P in ABF69196 (PubMed:16617059).Curated1
    Sequence conflicti438A → V in ABF69195 (PubMed:16617059).Curated1
    Sequence conflicti517S → P in ABF69195 (PubMed:16617059).Curated1
    Sequence conflicti575R → C in BAG61401 (PubMed:14702039).Curated1
    Sequence conflicti723G → E in BAG61401 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_027047191R → C1 PublicationCorresponds to variant dbSNP:rs3816533Ensembl.1
    Natural variantiVAR_027048239M → I. Corresponds to variant dbSNP:rs2290552Ensembl.1
    Natural variantiVAR_034365391R → H. Corresponds to variant dbSNP:rs34807597Ensembl.1
    Natural variantiVAR_060082591T → I. Corresponds to variant dbSNP:rs36126315Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0198711 – 299Missing in isoform 4. 1 PublicationAdd BLAST299
    Alternative sequenceiVSP_0393871 – 3MAV → MAEAALEAVRSELREFPAAA RELCVPLAVPYLDKPPTPLH FYRDWVCPNRPCIIRNALQH WPALQKWSLPYFRATVGSTE VSVAVTPDGYADAVRGDRFM MPAERRLPLSFVLDVLEGRA QHPGVLYVQKQCSNLPSELP QLLPDLESHVPWASEALGKM PDAVNFWLGEAAAVTSLHKD HYENLYCVVSGEKHFLFHPP SDRPFIPYELYTPATYQLTE EGTFKVVDEEAMEK in isoform 2, isoform 3 and isoform 5. 3 Publications3
    Alternative sequenceiVSP_039388641 – 765Missing in isoform 3. 1 PublicationAdd BLAST125
    Alternative sequenceiVSP_039389650 – 662QLQLL…CQEQG → GSGGHPRRRQLGR in isoform 2. 1 PublicationAdd BLAST13
    Alternative sequenceiVSP_039390663 – 781Missing in isoform 2. 1 PublicationAdd BLAST119

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF065215 mRNA Translation: AAC78836.1
    AF121908 mRNA Translation: AAD32135.1
    DQ523799 mRNA Translation: ABF69195.1
    DQ523800 mRNA Translation: ABF69196.1
    AK299419 mRNA Translation: BAG61401.1
    AB209150 mRNA Translation: BAD92387.1 Different initiation.
    AC020659 Genomic DNA No translation available.
    CCDSiCCDS45241.1
    RefSeqiNP_001108105.1, NM_001114633.1 [P0C869-1]
    NP_001185517.1, NM_001198588.1 [P0C869-7]
    NP_005081.1, NM_005090.3 [P0C869-6]
    UniGeneiHs.198161

    Genome annotation databases

    EnsembliENST00000452633; ENSP00000396045; ENSG00000243708 [P0C869-1]
    ENST00000458483; ENSP00000416610; ENSG00000243708 [P0C869-1]
    GeneIDi100137049
    8681
    KEGGihsa:100137049
    hsa:8681
    UCSCiuc010bco.4 human

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF065215 mRNA Translation: AAC78836.1
    AF121908 mRNA Translation: AAD32135.1
    DQ523799 mRNA Translation: ABF69195.1
    DQ523800 mRNA Translation: ABF69196.1
    AK299419 mRNA Translation: BAG61401.1
    AB209150 mRNA Translation: BAD92387.1 Different initiation.
    AC020659 Genomic DNA No translation available.
    CCDSiCCDS45241.1
    RefSeqiNP_001108105.1, NM_001114633.1 [P0C869-1]
    NP_001185517.1, NM_001198588.1 [P0C869-7]
    NP_005081.1, NM_005090.3 [P0C869-6]
    UniGeneiHs.198161

    3D structure databases

    ProteinModelPortaliP0C869
    SMRiP0C869
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114229, 2 interactors
    936685, 4 interactors
    IntActiP0C869, 3 interactors
    STRINGi9606.ENSP00000396045

    Chemistry databases

    BindingDBiP0C869
    ChEMBLiCHEMBL4136
    SwissLipidsiSLP:000000616 [P0C869-8]
    SLP:000000617 [P0C869-6]

    PTM databases

    iPTMnetiP0C869
    PhosphoSitePlusiP0C869

    Polymorphism and mutation databases

    BioMutaiPLA2G4B
    DMDMi300669659

    Proteomic databases

    EPDiP0C869
    MaxQBiP0C869
    PaxDbiP0C869
    PeptideAtlasiP0C869
    PRIDEiP0C869
    ProteomicsDBi52403
    52404 [P0C869-4]
    52405 [P0C869-6]
    52406 [P0C869-7]
    52407 [P0C869-8]

    Protocols and materials databases

    DNASUi8681
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000452633; ENSP00000396045; ENSG00000243708 [P0C869-1]
    ENST00000458483; ENSP00000416610; ENSG00000243708 [P0C869-1]
    GeneIDi100137049
    8681
    KEGGihsa:100137049
    hsa:8681
    UCSCiuc010bco.4 human

    Organism-specific databases

    CTDi100137049
    8681
    DisGeNETi100137049
    8681
    EuPathDBiHostDB:ENSG00000168970.21
    HostDB:ENSG00000243708.9
    GeneCardsiPLA2G4B
    HGNCiHGNC:9036 PLA2G4B
    HPAiHPA005726
    MIMi606088 gene
    neXtProtiNX_P0C869
    OpenTargetsiENSG00000168970
    ENSG00000243708
    PharmGKBiPA165479070
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1028 Eukaryota
    KOG1325 Eukaryota
    ENOG410XR72 LUCA
    GeneTreeiENSGT00550000074489
    HOVERGENiHBG080412
    InParanoidiP0C869
    KOiK16342
    OMAiFRFRIHS
    OrthoDBiEOG091G011T
    PhylomeDBiP0C869
    TreeFamiTF325228

    Enzyme and pathway databases

    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-1482925 Acyl chain remodelling of PG
    R-HSA-1483115 Hydrolysis of LPC
    R-HSA-1483166 Synthesis of PA
    R-HSA-381038 XBP1(S) activates chaperone genes

    Miscellaneous databases

    GeneWikiiPLA2G4B
    PROiPR:P0C869
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000168970 Expressed in 86 organ(s), highest expression level in right hemisphere of cerebellum
    ExpressionAtlasiP0C869 baseline and differential
    GenevisibleiP0C869 HS

    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
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPA24B_HUMAN
    AccessioniPrimary (citable) accession number: P0C869
    Secondary accession number(s): B4DRT9
    , O95712, Q19KD5, Q19KD6, Q59GF9, Q8TB10, Q9UKV7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 2, 2008
    Last sequence update: July 13, 2010
    Last modified: November 7, 2018
    This is version 93 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

    Complete proteome, Reference proteome

    Documents

    1. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    2. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
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