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O14939

- PLD2_HUMAN

UniProt

O14939 - PLD2_HUMAN

Protein

Phospholipase D2

Gene

PLD2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 2 (21 Feb 2001)
      Previous versions | rss
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    Functioni

    May have a role in signal-induced cytoskeletal regulation and/or endocytosis.By similarity

    Catalytic activityi

    A phosphatidylcholine + H2O = choline + a phosphatidate.

    Enzyme regulationi

    Stimulated by phosphatidylinositol 4,5-bisphosphate and activated by the ADP-ribosylation factor-1 (ARF-1).

    GO - Molecular functioni

    1. N-acylphosphatidylethanolamine-specific phospholipase D activity Source: UniProtKB-EC
    2. phosphatidylinositol binding Source: InterPro
    3. phospholipase D activity Source: ProtInc
    4. protein binding Source: IntAct

    GO - Biological processi

    1. cytoskeleton organization Source: ProtInc
    2. Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
    3. glycerophospholipid biosynthetic process Source: Reactome
    4. G-protein coupled receptor internalization Source: Ensembl
    5. innate immune response Source: Reactome
    6. lipid catabolic process Source: UniProtKB-KW
    7. phosphatidic acid biosynthetic process Source: Reactome
    8. phosphatidylglycerol biosynthetic process Source: Reactome
    9. phospholipid metabolic process Source: Reactome
    10. small GTPase mediated signal transduction Source: ProtInc
    11. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Lipid degradation, Lipid metabolism

    Enzyme and pathway databases

    BRENDAi3.1.4.4. 2681.
    ReactomeiREACT_120906. Synthesis of PA.
    REACT_121280. Synthesis of PG.
    REACT_160158. Role of phospholipids in phagocytosis.
    SignaLinkiO14939.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phospholipase D2 (EC:3.1.4.4)
    Short name:
    PLD 2
    Short name:
    hPLD2
    Alternative name(s):
    Choline phosphatase 2
    PLD1C
    Phosphatidylcholine-hydrolyzing phospholipase D2
    Gene namesi
    Name:PLD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:9068. PLD2.

    Subcellular locationi

    Membrane By similarity; Peripheral membrane protein By similarity

    GO - Cellular componenti

    1. brush border membrane Source: Ensembl
    2. endoplasmic reticulum membrane Source: Reactome
    3. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA33397.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 933933Phospholipase D2PRO_0000218805Add
    BLAST

    Post-translational modificationi

    Phosphorylated by FGR.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO14939.
    PaxDbiO14939.
    PRIDEiO14939.

    PTM databases

    PhosphoSiteiO14939.

    Expressioni

    Tissue specificityi

    Ubiquitous.

    Gene expression databases

    ArrayExpressiO14939.
    BgeeiO14939.
    CleanExiHS_PLD2.
    GenevestigatoriO14939.

    Organism-specific databases

    HPAiHPA013397.

    Interactioni

    Subunit structurei

    Interacts with EGFR By similarity. Interacts with PIP5K1B.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CFL1P235282EBI-1053996,EBI-352733
    GRB2P629934EBI-1053996,EBI-401755

    Protein-protein interaction databases

    BioGridi111354. 21 interactions.
    DIPiDIP-38903N.
    IntActiO14939. 3 interactions.
    MINTiMINT-141629.
    STRINGi9606.ENSP00000263088.

    Structurei

    3D structure databases

    ProteinModelPortaliO14939.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini65 – 195131PXPROSITE-ProRule annotationAdd
    BLAST
    Domaini203 – 311109PHAdd
    BLAST
    Domaini437 – 46428PLD phosphodiesterase 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini751 – 77828PLD phosphodiesterase 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni441 – 788348CatalyticAdd
    BLAST

    Sequence similaritiesi

    Belongs to the phospholipase D family.Curated
    Contains 1 PH domain.Curated
    Contains 2 PLD phosphodiesterase domains.PROSITE-ProRule annotation
    Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG1502.
    HOGENOMiHOG000246972.
    HOVERGENiHBG006650.
    InParanoidiO14939.
    KOiK01115.
    OMAiDWRLDVM.
    OrthoDBiEOG7N63KT.
    PhylomeDBiO14939.
    TreeFamiTF300589.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.30.1520.10. 1 hit.
    InterProiIPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001683. Phox.
    IPR025202. PLD-like_dom.
    IPR001736. PLipase_D/transphosphatidylase.
    IPR016555. PLipase_D_euk.
    IPR015679. PLipase_D_fam.
    [Graphical view]
    PANTHERiPTHR18896. PTHR18896. 1 hit.
    PfamiPF00614. PLDc. 1 hit.
    PF13091. PLDc_2. 1 hit.
    PF00787. PX. 1 hit.
    [Graphical view]
    PIRSFiPIRSF009376. Phospholipase_D_euk. 1 hit.
    SMARTiSM00233. PH. 1 hit.
    SM00155. PLDc. 2 hits.
    SM00312. PX. 1 hit.
    [Graphical view]
    SUPFAMiSSF64268. SSF64268. 1 hit.
    PROSITEiPS50035. PLD. 2 hits.
    PS50195. PX. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform PLD2A (identifier: O14939-1) [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

    MTATPESLFP TGDELDSSQL QMESDEVDTL KEGEDPADRM HPFLAIYELQ    50
    SLKVHPLVFA PGVPVTAQVV GTERYTSGSK VGTCTLYSVR LTHGDFSWTT 100
    KKKYRHFQEL HRDLLRHKVL MSLLPLARFA VAYSPARDAG NREMPSLPRA 150
    GPEGSTRHAA SKQKYLENYL NRLLTMSFYR NYHAMTEFLE VSQLSFIPDL 200
    GRKGLEGMIR KRSGGHRVPG LTCCGRDQVC YRWSKRWLVV KDSFLLYMCL 250
    ETGAISFVQL FDPGFEVQVG KRSTEARHGV RIDTSHRSLI LKCSSYRQAR 300
    WWAQEITELA QGPGRDFLQL HRHDSYAPPR PGTLARWFVN GAGYFAAVAD 350
    AILRAQEEIF ITDWWLSPEV YLKRPAHSDD WRLDIMLKRK AEEGVRVSIL 400
    LFKEVELALG INSGYSKRAL MLLHPNIKVM RHPDQVTLWA HHEKLLVVDQ 450
    VVAFLGGLDL AYGRWDDLHY RLTDLGDSSE SAASQPPTPR PDSPATPDLS 500
    HNQFFWLGKD YSNLITKDWV QLDRPFEDFI DRETTPRMPW RDVGVVVHGL 550
    PARDLARHFI QRWNFTKTTK AKYKTPTYPY LLPKSTSTAN QLPFTLPGGQ 600
    CTTVQVLRSV DRWSAGTLEN SILNAYLHTI RESQHFLYIE NQFFISCSDG 650
    RTVLNKVGDE IVDRILKAHK QGWCYRVYVL LPLLPGFEGD ISTGGGNSIQ 700
    AILHFTYRTL CRGEYSILHR LKAAMGTAWR DYISICGLRT HGELGGHPVS 750
    ELIYIHSKVL IADDRTVIIG SANINDRSLL GKRDSELAVL IEDTETEPSL 800
    MNGAEYQAGR FALSLRKHCF GVILGANTRP DLDLRDPICD DFFQLWQDMA 850
    ESNANIYEQI FRCLPSNATR SLRTLREYVA VEPLATVSPP LARSELTQVQ 900
    GHLVHFPLKF LEDESLLPPL GSKEGMIPLE VWT 933
    Length:933
    Mass (Da):105,987
    Last modified:February 21, 2001 - v2
    Checksum:iF25F6B73B45F57ED
    GO
    Isoform PLD2C (identifier: O14939-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         337-933: Missing.

    Show »
    Length:336
    Mass (Da):38,252
    Checksum:iB88330C3765169E3
    GO
    Isoform PLD2B (identifier: O14939-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         810-821: RFALSLRKHCFG → S

    Show »
    Length:922
    Mass (Da):104,657
    Checksum:iC160953BA88F8F19
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti16 – 161D → G in AAB96656. 1 PublicationCurated
    Sequence conflicti165 – 1651Y → C in AAB96656. 1 PublicationCurated
    Sequence conflicti212 – 2121R → C in AAB96656. 1 PublicationCurated
    Sequence conflicti268 – 2681Q → R in AAB96655. 1 PublicationCurated
    Sequence conflicti325 – 3251S → R in AAB96656. 1 PublicationCurated
    Sequence conflicti445 – 4451L → P in AAB96656. 1 PublicationCurated
    Sequence conflicti510 – 5101D → G in AAB96656. 1 PublicationCurated
    Sequence conflicti566 – 5661T → I in AAB96655. 1 PublicationCurated
    Sequence conflicti784 – 7841D → G in AAB96656. 1 PublicationCurated
    Sequence conflicti801 – 8022MN → ID in AAC24498. (PubMed:9582313)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti172 – 1721R → C.2 Publications
    Corresponds to variant rs2286672 [ dbSNP | Ensembl ].
    VAR_051704
    Natural varianti577 – 5771T → I.2 Publications
    Corresponds to variant rs1052748 [ dbSNP | Ensembl ].
    VAR_051705
    Natural varianti632 – 6321E → G.2 Publications
    Corresponds to variant rs17854914 [ dbSNP | Ensembl ].
    VAR_061750
    Natural varianti804 – 8041A → T.
    Corresponds to variant rs11545163 [ dbSNP | Ensembl ].
    VAR_051706
    Natural varianti807 – 8071Q → E in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036503
    Natural varianti821 – 8211G → R.
    Corresponds to variant rs3764897 [ dbSNP | Ensembl ].
    VAR_051707
    Natural varianti821 – 8211G → S.1 Publication
    Corresponds to variant rs3764897 [ dbSNP | Ensembl ].
    VAR_059774

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei337 – 933597Missing in isoform PLD2C. 1 PublicationVSP_005027Add
    BLAST
    Alternative sequencei810 – 82112RFALS…KHCFG → S in isoform PLD2B. 2 PublicationsVSP_054769Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF033850 mRNA. Translation: AAD04197.1.
    AF035483 mRNA. Translation: AAC24498.1.
    AF038440 mRNA. Translation: AAB96655.1.
    AF038441 mRNA. Translation: AAB96656.1.
    AC233723 Genomic DNA. No translation available.
    CH471108 Genomic DNA. Translation: EAW90405.1.
    BC015033 mRNA. Translation: AAH15033.1.
    BC056871 mRNA. Translation: AAH56871.1.
    CCDSiCCDS11057.1. [O14939-1]
    CCDS58507.1. [O14939-4]
    RefSeqiNP_001230037.1. NM_001243108.1. [O14939-4]
    NP_002654.3. NM_002663.4. [O14939-1]
    XP_006721610.1. XM_006721547.1. [O14939-1]
    UniGeneiHs.104519.

    Genome annotation databases

    EnsembliENST00000263088; ENSP00000263088; ENSG00000129219. [O14939-1]
    ENST00000572940; ENSP00000459571; ENSG00000129219. [O14939-4]
    GeneIDi5338.
    KEGGihsa:5338.
    UCSCiuc002fzc.3. human. [O14939-1]
    uc002fzd.3. human.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Phospholipase D entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF033850 mRNA. Translation: AAD04197.1 .
    AF035483 mRNA. Translation: AAC24498.1 .
    AF038440 mRNA. Translation: AAB96655.1 .
    AF038441 mRNA. Translation: AAB96656.1 .
    AC233723 Genomic DNA. No translation available.
    CH471108 Genomic DNA. Translation: EAW90405.1 .
    BC015033 mRNA. Translation: AAH15033.1 .
    BC056871 mRNA. Translation: AAH56871.1 .
    CCDSi CCDS11057.1. [O14939-1 ]
    CCDS58507.1. [O14939-4 ]
    RefSeqi NP_001230037.1. NM_001243108.1. [O14939-4 ]
    NP_002654.3. NM_002663.4. [O14939-1 ]
    XP_006721610.1. XM_006721547.1. [O14939-1 ]
    UniGenei Hs.104519.

    3D structure databases

    ProteinModelPortali O14939.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111354. 21 interactions.
    DIPi DIP-38903N.
    IntActi O14939. 3 interactions.
    MINTi MINT-141629.
    STRINGi 9606.ENSP00000263088.

    Chemistry

    BindingDBi O14939.
    ChEMBLi CHEMBL2734.
    DrugBanki DB00122. Choline.
    GuidetoPHARMACOLOGYi 1434.

    PTM databases

    PhosphoSitei O14939.

    Proteomic databases

    MaxQBi O14939.
    PaxDbi O14939.
    PRIDEi O14939.

    Protocols and materials databases

    DNASUi 5338.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000263088 ; ENSP00000263088 ; ENSG00000129219 . [O14939-1 ]
    ENST00000572940 ; ENSP00000459571 ; ENSG00000129219 . [O14939-4 ]
    GeneIDi 5338.
    KEGGi hsa:5338.
    UCSCi uc002fzc.3. human. [O14939-1 ]
    uc002fzd.3. human.

    Organism-specific databases

    CTDi 5338.
    GeneCardsi GC17P004710.
    H-InvDB HIX0013451.
    HGNCi HGNC:9068. PLD2.
    HPAi HPA013397.
    MIMi 602384. gene.
    neXtProti NX_O14939.
    PharmGKBi PA33397.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1502.
    HOGENOMi HOG000246972.
    HOVERGENi HBG006650.
    InParanoidi O14939.
    KOi K01115.
    OMAi DWRLDVM.
    OrthoDBi EOG7N63KT.
    PhylomeDBi O14939.
    TreeFami TF300589.

    Enzyme and pathway databases

    BRENDAi 3.1.4.4. 2681.
    Reactomei REACT_120906. Synthesis of PA.
    REACT_121280. Synthesis of PG.
    REACT_160158. Role of phospholipids in phagocytosis.
    SignaLinki O14939.

    Miscellaneous databases

    GeneWikii PLD2.
    GenomeRNAii 5338.
    NextBioi 20676.
    PROi O14939.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14939.
    Bgeei O14939.
    CleanExi HS_PLD2.
    Genevestigatori O14939.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.30.1520.10. 1 hit.
    InterProi IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001683. Phox.
    IPR025202. PLD-like_dom.
    IPR001736. PLipase_D/transphosphatidylase.
    IPR016555. PLipase_D_euk.
    IPR015679. PLipase_D_fam.
    [Graphical view ]
    PANTHERi PTHR18896. PTHR18896. 1 hit.
    Pfami PF00614. PLDc. 1 hit.
    PF13091. PLDc_2. 1 hit.
    PF00787. PX. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF009376. Phospholipase_D_euk. 1 hit.
    SMARTi SM00233. PH. 1 hit.
    SM00155. PLDc. 2 hits.
    SM00312. PX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF64268. SSF64268. 1 hit.
    PROSITEi PS50035. PLD. 2 hits.
    PS50195. PX. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of human PLD2 and the analysis of PLD isoform splice variants."
      Steed P.M., Clark K.L., Boyar W.C., Lasala D.J.
      FASEB J. 12:1309-1317(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PLD2A; PLD2B AND PLD2C), CHARACTERIZATION, VARIANT CYS-172.
      Tissue: Brain.
    2. "Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2."
      Lopez I., Arnold R.S., Lambeth J.D.
      J. Biol. Chem. 273:12846-12852(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLD2A), CHARACTERIZATION, VARIANT ILE-577.
      Tissue: B-cell.
    3. Saqib K.M., Clark J.M., Byrd P.J., Armstrong S.J., Wakelam M.J.O.
      Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PLD2A AND PLD2B), VARIANTS GLY-632 AND SER-821.
    4. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORM PLD2A), VARIANTS CYS-172; ILE-577 AND GLY-632.
      Tissue: Skin and Uterus.
    7. "Interaction of the type Ialpha PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4, 5-bisphosphate in the regulation of PLD2 activity."
      Divecha N., Roefs M., Halstead J.R., D'Andrea S., Fernandez-Borga M., Oomen L., Saqib K.M., Wakelam M.J.O., D'Santos C.
      EMBO J. 19:5440-5449(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIP5K1B.
    8. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-807.

    Entry informationi

    Entry nameiPLD2_HUMAN
    AccessioniPrimary (citable) accession number: O14939
    Secondary accession number(s): I3L2C9
    , O43540, O43579, O43580, Q6PGR0, Q96BY3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: February 21, 2001
    Last modified: October 1, 2014
    This is version 141 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 17
      Human chromosome 17: 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