ID   PLD2_MOUSE              Reviewed;         933 AA.
AC   P97813;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 2.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Phospholipase D2 {ECO:0000305};
DE            Short=PLD 2;
DE            Short=mPLD2;
DE            EC=3.1.4.4 {ECO:0000269|PubMed:21085684};
DE   AltName: Full=Choline phosphatase 2;
DE   AltName: Full=PLD1C;
DE   AltName: Full=Phosphatidylcholine-hydrolyzing phospholipase D2;
GN   Name=Pld2 {ECO:0000312|MGI:MGI:892877};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, SUBCELLULAR LOCATION,
RP   AND ACTIVITY REGULATION.
RC   TISSUE=Embryo, and Neonatal brain;
RX   PubMed=9395408; DOI=10.1016/s0960-9822(97)70090-3;
RA   Colley W.C., Sung T.-C., Roll R., Jenco J.M., Hammond S.M.,
RA   Altshuller Y.M., Bar-Sagi D., Morris A.J., Frohman M.A.;
RT   "Phospholipase D2, a distinct phospholipase D isoform with novel regulatory
RT   properties that provokes cytoskeletal reorganization.";
RL   Curr. Biol. 7:191-201(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129;
RX   PubMed=9560313; DOI=10.1042/bj3310845;
RA   Redina O.E., Frohman M.A.;
RT   "Organization and alternative splicing of the murine phospholipase D2
RT   gene.";
RL   Biochem. J. 331:845-851(1998).
RN   [3]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=9307024; DOI=10.1042/bj3260745;
RA   Colley W.C., Altshuller Y.M., Sue-Ling C.K., Copeland N.G., Gilbert D.J.,
RA   Jenkins N.A., Branch K.D., Tsirka S.E., Bollag R.J., Bollag W.B.,
RA   Frohman M.A.;
RT   "Cloning and expression analysis of murine phospholipase D1.";
RL   Biochem. J. 326:745-753(1997).
RN   [4]
RP   PHOSPHORYLATION AT TYR-11, MUTAGENESIS OF TYR-11, AND INTERACTION WITH
RP   EGFR.
RX   PubMed=9837959; DOI=10.1074/jbc.273.50.33722;
RA   Slaaby R., Jensen T., Hansen H.S., Frohman M.A., Seedorf K.;
RT   "PLD2 complexes with the EGF receptor and undergoes tyrosine
RT   phosphorylation at a single site upon agonist stimulation.";
RL   J. Biol. Chem. 273:33722-33727(1998).
RN   [5]
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
RX   PubMed=21085684; DOI=10.1371/journal.pone.0013932;
RA   Yoshikawa F., Banno Y., Otani Y., Yamaguchi Y., Nagakura-Takagi Y.,
RA   Morita N., Sato Y., Saruta C., Nishibe H., Sadakata T., Shinoda Y.,
RA   Hayashi K., Mishima Y., Baba H., Furuichi T.;
RT   "Phospholipase D family member 4, a transmembrane glycoprotein with no
RT   phospholipase D activity, expression in spleen and early postnatal
RT   microglia.";
RL   PLoS ONE 5:E13932-E13932(2010).
CC   -!- FUNCTION: Function as phospholipase selective for phosphatidylcholine
CC       (PubMed:21085684). May have a role in signal-induced cytoskeletal
CC       regulation and/or endocytosis (PubMed:9395408).
CC       {ECO:0000269|PubMed:21085684, ECO:0000269|PubMed:9395408}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-
CC         sn-glycero-3-phosphate + choline + H(+); Xref=Rhea:RHEA:14445,
CC         ChEBI:CHEBI:15354, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57643, ChEBI:CHEBI:58608; EC=3.1.4.4;
CC         Evidence={ECO:0000269|PubMed:21085684};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14446;
CC         Evidence={ECO:0000305|PubMed:21085684};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-
CC         dihexadecanoyl-sn-glycero-3-phosphate + choline + H(+);
CC         Xref=Rhea:RHEA:44872, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:72859, ChEBI:CHEBI:72999;
CC         Evidence={ECO:0000269|PubMed:21085684};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44873;
CC         Evidence={ECO:0000305|PubMed:21085684};
CC   -!- ACTIVITY REGULATION: Stimulated by phosphatidylinositol 4,5-
CC       bisphosphate. Is not responsive to either ADP-ribosylation factor-1
CC       (ARF-1) or GTP-binding proteins such as RHOA.
CC       {ECO:0000269|PubMed:9395408}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7.4. {ECO:0000269|PubMed:21085684};
CC   -!- SUBUNIT: Interacts with PIP5K1B (By similarity). Interacts with EGFR
CC       (PubMed:9837959). {ECO:0000250|UniProtKB:O14939,
CC       ECO:0000269|PubMed:9837959}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9395408};
CC       Lipid-anchor {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=1;
CC         Comment=At least 3 isoforms are produced.;
CC       Name=1;
CC         IsoId=P97813-1; Sequence=Displayed;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels in brain and lung.
CC       {ECO:0000269|PubMed:9307024}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at high levels in the hippocampus at the
CC       earliest time at which it is defined as a structure and also in
CC       ventricular neural cells as well as differentiating neurons outside of
CC       the ventricular region. Expressed during development in lower levels in
CC       mesenchymal cells derived from the neural crest that are destined to
CC       form bones of the skull. {ECO:0000269|PubMed:9307024}.
CC   -!- PTM: Phosphorylated by FGR (By similarity). Phosphorylated on Tyr-11;
CC       most likely by EGFR (PubMed:9837959). {ECO:0000250|UniProtKB:P70498,
CC       ECO:0000269|PubMed:9837959}.
CC   -!- SIMILARITY: Belongs to the phospholipase D family. {ECO:0000305}.
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DR   EMBL; U87557; AAC53173.1; -; mRNA.
DR   EMBL; AF052294; AAC24519.1; -; Genomic_DNA.
DR   EMBL; AF052291; AAC24519.1; JOINED; Genomic_DNA.
DR   EMBL; AF052293; AAC24519.1; JOINED; Genomic_DNA.
DR   EMBL; AF052292; AAC24519.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS24953.1; -. [P97813-1]
DR   RefSeq; NP_032902.1; NM_008876.3. [P97813-1]
DR   RefSeq; XP_011247096.1; XM_011248794.2. [P97813-1]
DR   AlphaFoldDB; P97813; -.
DR   SMR; P97813; -.
DR   BioGRID; 202240; 3.
DR   CORUM; P97813; -.
DR   STRING; 10090.ENSMUSP00000104197; -.
DR   ChEMBL; CHEMBL3309055; -.
DR   SwissLipids; SLP:000001045; -.
DR   iPTMnet; P97813; -.
DR   PhosphoSitePlus; P97813; -.
DR   SwissPalm; P97813; -.
DR   PaxDb; 10090-ENSMUSP00000018429; -.
DR   PeptideAtlas; P97813; -.
DR   ProteomicsDB; 288233; -. [P97813-1]
DR   Antibodypedia; 2859; 312 antibodies from 34 providers.
DR   DNASU; 18806; -.
DR   Ensembl; ENSMUST00000018429.12; ENSMUSP00000018429.6; ENSMUSG00000020828.14. [P97813-1]
DR   GeneID; 18806; -.
DR   KEGG; mmu:18806; -.
DR   UCSC; uc007jvg.2; mouse. [P97813-1]
DR   AGR; MGI:892877; -.
DR   CTD; 5338; -.
DR   MGI; MGI:892877; Pld2.
DR   VEuPathDB; HostDB:ENSMUSG00000020828; -.
DR   eggNOG; KOG1329; Eukaryota.
DR   GeneTree; ENSGT00940000160229; -.
DR   HOGENOM; CLU_000690_2_0_1; -.
DR   InParanoid; P97813; -.
DR   OrthoDB; 335467at2759; -.
DR   TreeFam; TF300589; -.
DR   BRENDA; 3.1.4.4; 3474.
DR   Reactome; R-MMU-1483166; Synthesis of PA.
DR   Reactome; R-MMU-2029485; Role of phospholipids in phagocytosis.
DR   Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR   Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR   BioGRID-ORCS; 18806; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Pld2; mouse.
DR   PRO; PR:P97813; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P97813; Protein.
DR   Bgee; ENSMUSG00000020828; Expressed in lip and 180 other cell types or tissues.
DR   ExpressionAtlas; P97813; baseline and differential.
DR   GO; GO:0031526; C:brush border membrane; IDA:MGI.
DR   GO; GO:0005901; C:caveola; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0030027; C:lamellipodium; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR   GO; GO:0070290; F:N-acylphosphatidylethanolamine-specific phospholipase D activity; IEA:UniProtKB-EC.
DR   GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR   GO; GO:0004630; F:phospholipase D activity; IDA:MGI.
DR   GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR   GO; GO:0002031; P:G protein-coupled receptor internalization; IDA:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR   GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR   GO; GO:0006654; P:phosphatidic acid biosynthetic process; IEA:InterPro.
DR   GO; GO:0009395; P:phospholipid catabolic process; ISO:MGI.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR   GO; GO:0043306; P:positive regulation of mast cell degranulation; ISO:MGI.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI.
DR   GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISO:MGI.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; IDA:MGI.
DR   GO; GO:0060627; P:regulation of vesicle-mediated transport; IBA:GO_Central.
DR   GO; GO:0042542; P:response to hydrogen peroxide; ISO:MGI.
DR   GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR   GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR   GO; GO:0043434; P:response to peptide hormone; ISO:MGI.
DR   CDD; cd01254; PH_PLD; 1.
DR   Gene3D; 3.30.870.10; Endonuclease Chain A; 2.
DR   Gene3D; 3.30.1520.10; Phox-like domain; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   InterPro; IPR025202; PLD-like_dom.
DR   InterPro; IPR001736; PLipase_D/transphosphatidylase.
DR   InterPro; IPR016555; PLipase_D_euk.
DR   InterPro; IPR015679; PLipase_D_fam.
DR   InterPro; IPR001683; PX_dom.
DR   InterPro; IPR036871; PX_dom_sf.
DR   PANTHER; PTHR18896; PHOSPHOLIPASE D; 1.
DR   PANTHER; PTHR18896:SF121; PHOSPHOLIPASE D2; 1.
DR   Pfam; PF00614; PLDc; 1.
DR   Pfam; PF13091; PLDc_2; 1.
DR   Pfam; PF00787; PX; 1.
DR   PIRSF; PIRSF009376; Phospholipase_D_euk; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00155; PLDc; 2.
DR   SMART; SM00312; PX; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF56024; Phospholipase D/nuclease; 2.
DR   SUPFAM; SSF64268; PX domain; 1.
DR   PROSITE; PS50035; PLD; 2.
DR   PROSITE; PS50195; PX; 1.
DR   Genevisible; P97813; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Hydrolase; Lipid degradation;
KW   Lipid metabolism; Lipoprotein; Membrane; Phosphoprotein;
KW   Reference proteome; Repeat.
FT   CHAIN           1..933
FT                   /note="Phospholipase D2"
FT                   /id="PRO_0000218806"
FT   DOMAIN          65..195
FT                   /note="PX"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT   DOMAIN          203..311
FT                   /note="PH"
FT   DOMAIN          437..464
FT                   /note="PLD phosphodiesterase 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT   DOMAIN          751..778
FT                   /note="PLD phosphodiesterase 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT   REGION          441..788
FT                   /note="Catalytic"
FT   MOD_RES         11
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:9837959"
FT   MUTAGEN         11
FT                   /note="Y->F: 2-fold increase in basal phospholipase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:9837959"
SQ   SEQUENCE   933 AA;  106168 MW;  BADE1E0DF2EAC9ED CRC64;
     MTVTQKNLFP YGDYLNSSQL HMEPDEVDTL REGEDPADRM HPYLAIYDLQ PLKAHPLVFA
     PGVPVIAQVV GTERYTSGSK VGTCTLYSVR LTHGDFTWTT KKKFRHFQEL HRDLQRHKVL
     MSLLPLARFA VTHSPAREAA AEDIPSLPRG GSEGSARHTA SKQKYLENYL NRLLTMSFYR
     NYHAMTEFLE VSQLSFIPDL GSKGLEGVIR KRSGGHRVPG FTFCGRDQVC YRWSKRWLVV
     KDSFLLYMRP ETGAISFVQL FDPGFEVQVG KRSTETRYGV RIDTSHRSLI LKCSSYRQAR
     WWGQEITELA QGSGRDFLQL HQHDSYAPPR PGTLARWFVN GAGYFAAVAD AILRAQEEIF
     ITDWWLSPEI YLKRPAHSDD WRLDIMLKRK AEEGVRVSIL LFKEVELALG INSGYSKRTL
     MLLHPNIKVM RHPDLVTLWA HHEKLLVVDQ VVAFLGGLDL AFGRWDDVQY RLTDLGDPSE
     PVHLQTPTLG SDPAATPDLS HNQFFWLGKD YSNLITKDWV QLDRPFEDFI DRETTPRMPW
     RDVGVVVHGV AARDLARHFI QRWNFTKTTK ARYKTPLYPY LLPKSTSTAN NLPFMIPGGQ
     CATVQVLRSV DRWSAGTLEN SILNAYLHTI RESQHFLYIE NQFFISCSDG RTVLNKVGDE
     IVDRILKAHE QGQCFRVYLL LPLLPGFEGD ISTGGGNSIQ AILHFTYRTL CRGEHSILHR
     LKAAMGTAWR DYMSICGLRT HGELGGHPIS ELIYIHSKML IADDRTVIIG SANINDRSLL
     GKRDSELAIL IKDTEMEPSL MDGVEYQAGR FALSLRKHCF SVILGANTWP DLDLRDPVCD
     DFFQLWQETA ENNATIYEQI FRCLPSNATR SLRALREYVA VESLATVSPS LAQSELAHIQ
     GHLVHFPLKF LEDESLLPPL GSKEGMIPLE VWT
//