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Q86XP0

- PA24D_HUMAN

UniProt

Q86XP0 - PA24D_HUMAN

Protein

Cytosolic phospholipase A2 delta

Gene

PLA2G4D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 98 (01 Oct 2014)
      Sequence version 2 (24 Nov 2009)
      Previous versions | rss
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    Functioni

    Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position. Not arachidonic acid-specific but has linoleic acid-specific activity. May play a role in inflammation in psoriatic lesions.1 Publication

    Catalytic activityi

    Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.

    Enzyme regulationi

    Stimulated by cytosolic Ca2+.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei361 – 3611NucleophileBy similarity
    Active sitei647 – 6471Proton acceptorBy similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. phospholipase A2 activity Source: UniProtKB-EC

    GO - Biological processi

    1. glycerophospholipid biosynthetic process Source: Reactome
    2. phosphatidic acid biosynthetic process Source: Reactome
    3. phosphatidylcholine acyl-chain remodeling Source: Reactome
    4. phosphatidylethanolamine acyl-chain remodeling Source: Reactome
    5. phosphatidylglycerol acyl-chain remodeling Source: Reactome
    6. phosphatidylinositol acyl-chain remodeling Source: Reactome
    7. phosphatidylserine acyl-chain remodeling Source: Reactome
    8. phospholipid catabolic process Source: InterPro
    9. phospholipid metabolic process Source: Reactome
    10. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Lipid degradation, Lipid metabolism

    Keywords - Ligandi

    Calcium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_120722. Acyl chain remodelling of PI.
    REACT_120829. Acyl chain remodelling of PC.
    REACT_120906. Synthesis of PA.
    REACT_120977. Hydrolysis of LPC.
    REACT_121324. Acyl chain remodelling of PG.
    REACT_121369. Acyl chain remodelling of PE.
    REACT_121384. Acyl chain remodelling of PS.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytosolic phospholipase A2 delta (EC:3.1.1.4)
    Short name:
    cPLA2-delta
    Alternative name(s):
    Phospholipase A2 group IVD
    Gene namesi
    Name:PLA2G4D
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:30038. PLA2G4D.

    Subcellular locationi

    Cytoplasmcytosol. Cytoplasmic vesicle membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
    Note: Translocates to membrane vesicles in a calcium-dependent fashion. Translocates to perinuclear regions upon ionomycin stimulation By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasmic vesicle membrane Source: UniProtKB-SubCell
    2. cytosol Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm, Cytoplasmic vesicle, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134974074.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 818818Cytosolic phospholipase A2 deltaPRO_0000247023Add
    BLAST

    Proteomic databases

    MaxQBiQ86XP0.
    PaxDbiQ86XP0.
    PRIDEiQ86XP0.

    PTM databases

    PhosphoSiteiQ86XP0.

    Expressioni

    Tissue specificityi

    Expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. Strongly expressed in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin.1 Publication

    Gene expression databases

    BgeeiQ86XP0.
    CleanExiHS_PLA2G4D.
    GenevestigatoriQ86XP0.

    Organism-specific databases

    HPAiHPA039489.

    Interactioni

    Protein-protein interaction databases

    BioGridi129664. 1 interaction.
    STRINGi9606.ENSP00000290472.

    Structurei

    3D structure databases

    ProteinModelPortaliQ86XP0.
    SMRiQ86XP0. Positions 23-166, 234-807.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini9 – 120112C2PROSITE-ProRule annotationAdd
    BLAST
    Domaini273 – 818546PLA2cPROSITE-ProRule annotationAdd
    BLAST

    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

    Sequence similaritiesi

    Contains 1 C2 domain.PROSITE-ProRule annotation
    Contains 1 PLA2c domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG300348.
    HOGENOMiHOG000231788.
    HOVERGENiHBG080412.
    InParanoidiQ86XP0.
    KOiK16342.
    OMAiTYKEEDF.
    OrthoDBiEOG70CR62.
    PhylomeDBiQ86XP0.
    TreeFamiTF325228.

    Family and domain databases

    Gene3Di2.60.40.150. 1 hit.
    InterProiIPR016035. Acyl_Trfase/lysoPLipase.
    IPR000008. C2_dom.
    IPR002642. LysoPLipase_cat_dom.
    [Graphical view]
    PfamiPF00168. C2. 1 hit.
    PF01735. PLA2_B. 1 hit.
    [Graphical view]
    SMARTiSM00239. C2. 1 hit.
    SM00022. PLAc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49562. SSF49562. 1 hit.
    SSF52151. SSF52151. 1 hit.
    PROSITEiPS50004. C2. 1 hit.
    PS51210. PLA2C. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q86XP0-1) [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

    MESLSPGGPP GHPYQGEAST CWQLTVRVLE ARNLRWADLL SEADPYVILQ    50
    LSTAPGMKFK TKTLTDTSHP VWNEAFRFLI QSQVKNVLEL SIYDEDSVTE 100
    DDICFKVLYD ISEVLPGKLL RKTFSQSPQG EEELDVEFLM EETSDRPENL 150
    ITNKVIVARE LSCLDVHLDS TGSTAVVADQ DKLELELVLK GSYEDTQTSF 200
    LGTASAFRFH YMAALETELS GRLRSSRSNG WNGDNSAGYL TVPLRPLTIG 250
    KEVTMDVPAP NAPGVRLQLK AEGCPEELAV HLGFNLCAEE QAFLSRRKQV 300
    VAKALKQALQ LDRDLQEDEV PVVGIMATGG GARAMTSLYG HLLALQKLGL 350
    LDCVTYFSGI SGSTWTMAHL YGDPEWSQRD LEGPIRYARE HLAKSKLEVF 400
    SPERLASYRR ELELRAEQGH PTTFVDLWAL VLESMLHGQV MDQKLSGQRA 450
    ALERGQNPLP LYLSLNVKEN NLETLDFKEW VEFSPYEVGF LKYGAFVPPE 500
    LFGSEFFMGR LMRRIPEPRI CFLEAIWSNI FSLNLLDAWY DLTSSGESWK 550
    QHIKDKTRSL EKEPLTTSGT SSRLEASWLQ PGTALAQAFK GFLTGRPLHQ 600
    RSPNFLQGLQ LHQDYCSHKD FSTWADYQLD SMPSQLTPKE PRLCLVDAAY 650
    FINTSSPSMF RPGRRLDLIL SFDYSLSAPF EALQQTELYC RARGLPFPRV 700
    EPSPQDQHQP RECHLFSDPA CPEAPILLHF PLVNASFKDH SAPGVQRSPA 750
    ELQGGQVDLT GATCPYTLSN MTYKEEDFER LLRLSDYNVQ TSQGAILQAL 800
    RTALKHRTLE ARPPRAQT 818
    Length:818
    Mass (Da):91,952
    Last modified:November 24, 2009 - v2
    Checksum:i06187324748A4C21
    GO
    Isoform 2 (identifier: Q86XP0-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         682-723: ALQQTELYCR...HLFSDPACPE → VPWSPQGNPS...VPKGRRGVRP
         724-818: Missing.

    Note: May be due to an intron retention.Curated

    Show »
    Length:723
    Mass (Da):80,930
    Checksum:i0C385309D4BAB085
    GO

    Sequence cautioni

    The sequence AAH34571.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti10 – 101P → T in BAC67158. (PubMed:14709560)Curated
    Isoform 2 (identifier: Q86XP0-2)
    Sequence conflicti713 – 7131G → R in AAH34571. (PubMed:16572171)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti275 – 2751P → R.
    Corresponds to variant rs11635685 [ dbSNP | Ensembl ].
    VAR_057676
    Natural varianti434 – 4341S → T.
    Corresponds to variant rs4924618 [ dbSNP | Ensembl ].
    VAR_057677
    Natural varianti573 – 5731R → W.
    Corresponds to variant rs17747505 [ dbSNP | Ensembl ].
    VAR_027049
    Natural varianti649 – 6491A → G.
    Corresponds to variant rs17690899 [ dbSNP | Ensembl ].
    VAR_027050
    Natural varianti747 – 7471R → G.1 Publication
    Corresponds to variant rs2459692 [ dbSNP | Ensembl ].
    VAR_027051
    Natural varianti783 – 7831R → Q.
    Corresponds to variant rs750052 [ dbSNP | Ensembl ].
    VAR_057678
    Natural varianti807 – 8071R → Q.
    Corresponds to variant rs750051 [ dbSNP | Ensembl ].
    VAR_057679

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei682 – 72342ALQQT…PACPE → VPWSPQGNPSAQPGQAPEAS SRATEPLPHTAGVPKGRRGV RP in isoform 2. 1 PublicationVSP_019881Add
    BLAST
    Alternative sequencei724 – 81895Missing in isoform 2. 1 PublicationVSP_019882Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB090876 mRNA. Translation: BAC67158.1.
    AC084693 Genomic DNA. No translation available.
    BC034571 mRNA. Translation: AAH34571.1. Different initiation.
    CCDSiCCDS32203.1. [Q86XP0-1]
    RefSeqiNP_828848.3. NM_178034.3. [Q86XP0-1]
    UniGeneiHs.380225.

    Genome annotation databases

    EnsembliENST00000290472; ENSP00000290472; ENSG00000159337. [Q86XP0-1]
    GeneIDi283748.
    KEGGihsa:283748.
    UCSCiuc001zox.3. human. [Q86XP0-1]

    Polymorphism databases

    DMDMi269849641.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB090876 mRNA. Translation: BAC67158.1 .
    AC084693 Genomic DNA. No translation available.
    BC034571 mRNA. Translation: AAH34571.1 . Different initiation.
    CCDSi CCDS32203.1. [Q86XP0-1 ]
    RefSeqi NP_828848.3. NM_178034.3. [Q86XP0-1 ]
    UniGenei Hs.380225.

    3D structure databases

    ProteinModelPortali Q86XP0.
    SMRi Q86XP0. Positions 23-166, 234-807.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 129664. 1 interaction.
    STRINGi 9606.ENSP00000290472.

    PTM databases

    PhosphoSitei Q86XP0.

    Polymorphism databases

    DMDMi 269849641.

    Proteomic databases

    MaxQBi Q86XP0.
    PaxDbi Q86XP0.
    PRIDEi Q86XP0.

    Protocols and materials databases

    DNASUi 283748.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000290472 ; ENSP00000290472 ; ENSG00000159337 . [Q86XP0-1 ]
    GeneIDi 283748.
    KEGGi hsa:283748.
    UCSCi uc001zox.3. human. [Q86XP0-1 ]

    Organism-specific databases

    CTDi 283748.
    GeneCardsi GC15M042359.
    H-InvDB HIX0026772.
    HGNCi HGNC:30038. PLA2G4D.
    HPAi HPA039489.
    MIMi 612864. gene.
    neXtProti NX_Q86XP0.
    PharmGKBi PA134974074.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG300348.
    HOGENOMi HOG000231788.
    HOVERGENi HBG080412.
    InParanoidi Q86XP0.
    KOi K16342.
    OMAi TYKEEDF.
    OrthoDBi EOG70CR62.
    PhylomeDBi Q86XP0.
    TreeFami TF325228.

    Enzyme and pathway databases

    Reactomei REACT_120722. Acyl chain remodelling of PI.
    REACT_120829. Acyl chain remodelling of PC.
    REACT_120906. Synthesis of PA.
    REACT_120977. Hydrolysis of LPC.
    REACT_121324. Acyl chain remodelling of PG.
    REACT_121369. Acyl chain remodelling of PE.
    REACT_121384. Acyl chain remodelling of PS.

    Miscellaneous databases

    GenomeRNAii 283748.
    NextBioi 94215.
    PROi Q86XP0.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q86XP0.
    CleanExi HS_PLA2G4D.
    Genevestigatori Q86XP0.

    Family and domain databases

    Gene3Di 2.60.40.150. 1 hit.
    InterProi IPR016035. Acyl_Trfase/lysoPLipase.
    IPR000008. C2_dom.
    IPR002642. LysoPLipase_cat_dom.
    [Graphical view ]
    Pfami PF00168. C2. 1 hit.
    PF01735. PLA2_B. 1 hit.
    [Graphical view ]
    SMARTi SM00239. C2. 1 hit.
    SM00022. PLAc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 1 hit.
    SSF52151. SSF52151. 1 hit.
    PROSITEi PS50004. C2. 1 hit.
    PS51210. PLA2C. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2delta, induced in psoriatic skin."
      Chiba H., Michibata H., Wakimoto K., Seishima M., Kawasaki S., Okubo K., Mitsui H., Torii H., Imai Y.
      J. Biol. Chem. 279:12890-12897(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
    2. "Analysis of the DNA sequence and duplication history of human chromosome 15."
      Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
      , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
      Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 491-818 (ISOFORM 2).
      Tissue: Brain.
    4. "A family based study of the genetic association between the PLA2G4D gene and schizophrenia."
      Tao R., Yu Y., Zhang X., Shi J., Guo Y., Wang C., Han B., Xu Q., Shang H., Zhang X., Xie L., Liu S., Ju G., Shen Y., Wei J.
      Prostaglandins Leukot. Essent. Fatty Acids 73:419-422(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT GLY-747.

    Entry informationi

    Entry nameiPA24D_HUMAN
    AccessioniPrimary (citable) accession number: Q86XP0
    Secondary accession number(s): Q8N176
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 25, 2006
    Last sequence update: November 24, 2009
    Last modified: October 1, 2014
    This is version 98 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 15
      Human chromosome 15: 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

    External Data

    Dasty 3