PLD2_MOUSE
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 03-AUG-2022, entry version 177.
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.ENSMUSP00000018429; -.
DR ChEMBL; CHEMBL3309055; -.
DR SwissLipids; SLP:000001045; -.
DR iPTMnet; P97813; -.
DR PhosphoSitePlus; P97813; -.
DR SwissPalm; P97813; -.
DR PaxDb; P97813; -.
DR PeptideAtlas; P97813; -.
DR PRIDE; P97813; -.
DR ProteomicsDB; 288233; -. [P97813-1]
DR Antibodypedia; 2859; 288 antibodies from 34 providers.
DR DNASU; 18806; -.
DR Ensembl; ENSMUST00000018429; ENSMUSP00000018429; ENSMUSG00000020828. [P97813-1]
DR GeneID; 18806; -.
DR KEGG; mmu:18806; -.
DR UCSC; uc007jvg.2; mouse. [P97813-1]
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 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 74 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 176 other tissues.
DR ExpressionAtlas; P97813; baseline and differential.
DR Genevisible; P97813; MM.
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:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0030027; C:lamellipodium; ISO:MGI.
DR GO; GO:0005634; C:nucleus; 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:0048017; P:inositol lipid-mediated signaling; 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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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 Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.1520.10; -; 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; PTHR18896; 2.
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; SSF64268; SSF64268; 1.
DR PROSITE; PS50035; PLD; 2.
DR PROSITE; PS50195; PX; 1.
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
