PLD3_RAT
ID PLD3_RAT Reviewed; 488 AA.
AC Q5FVH2;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=5'-3' exonuclease PLD3;
DE EC=3.1.16.1 {ECO:0000250|UniProtKB:Q8IV08};
DE AltName: Full=Choline phosphatase 3;
DE AltName: Full=Phosphatidylcholine-hydrolyzing phospholipase D3;
DE AltName: Full=Phospholipase D3;
DE Short=PLD 3;
GN Name=Pld3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-385, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: 5'->3' DNA exonuclease which digests single-stranded DNA
CC (ssDNA) (By similarity). Regulates inflammatory cytokine responses via
CC the degradation of nucleic acids, by reducing the concentration of
CC ssDNA able to stimulate TLR9, a nucleotide-sensing receptor in
CC collaboration with PLD4 (By similarity). May be important in myotube
CC formation. Plays a role in lysosomal homeostasis. Involved in the
CC regulation of endosomal protein sorting (By similarity).
CC {ECO:0000250|UniProtKB:O35405, ECO:0000250|UniProtKB:Q8IV08}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 5'- to 3'-direction to yield
CC nucleoside 3'-phosphates.; EC=3.1.16.1;
CC Evidence={ECO:0000250|UniProtKB:Q8IV08};
CC -!- SUBUNIT: Interacts with APP. {ECO:0000250|UniProtKB:Q8IV08}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8IV08}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q8IV08}. Lysosome lumen
CC {ECO:0000250|UniProtKB:Q8IV08}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q8IV08}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q8IV08}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q8IV08}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q8IV08}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q8IV08}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q8IV08}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q8IV08}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q8IV08}. Note=Localizes to ER-associated
CC vesicles in differentiating myotubes. The soluble form in lysosome
CC arises by proteolytic processing of the membrane-bound form.
CC {ECO:0000250|UniProtKB:Q8IV08}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8IV08}.
CC -!- PTM: Proteolytically processed to a soluble form that is stable within
CC endosomes and lysosomes. During transport through the secretory pathway
CC becomes proteolysed by cysteine proteases, thereby releasing a stable
CC soluble lysosomal lumenal polypeptide, whereas the transmembrane-bound
CC fragment is rapidly degraded. Its transport route to lysosomes involves
CC ubiquitination and the ESCRT complex. {ECO:0000250|UniProtKB:Q8IV08}.
CC -!- PTM: Ubiquitinated. Ubiquitination mediates sorting into lysosomes.
CC {ECO:0000250|UniProtKB:Q8IV08}.
CC -!- SIMILARITY: Belongs to the phospholipase D family. {ECO:0000305}.
CC -!- CAUTION: It was initially thought that PDL3 has phospholipase D
CC activity due to its HKD motifs. The second HKD motif contains Glu
CC instead of the canonical Asp. Its enzyme activity is therefore unsure.
CC Catalytic phospholipase D activity is still controversial (By
CC similarity). Its closest homolog PLD4, exhibits no phospholipase
CC activity (By similarity). {ECO:0000250|UniProtKB:O35405,
CC ECO:0000250|UniProtKB:Q8BG07}.
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DR EMBL; BC089987; AAH89987.1; -; mRNA.
DR RefSeq; NP_001012167.1; NM_001012167.1.
DR RefSeq; XP_006228640.1; XM_006228578.3.
DR RefSeq; XP_006228641.1; XM_006228579.3.
DR RefSeq; XP_006228642.1; XM_006228580.2.
DR RefSeq; XP_006228643.1; XM_006228581.3.
DR AlphaFoldDB; Q5FVH2; -.
DR SMR; Q5FVH2; -.
DR BioGRID; 262748; 1.
DR IntAct; Q5FVH2; 2.
DR STRING; 10116.ENSRNOP00000054004; -.
DR GlyGen; Q5FVH2; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q5FVH2; -.
DR PhosphoSitePlus; Q5FVH2; -.
DR jPOST; Q5FVH2; -.
DR PaxDb; Q5FVH2; -.
DR PRIDE; Q5FVH2; -.
DR Ensembl; ENSRNOT00000057177; ENSRNOP00000054004; ENSRNOG00000018390.
DR GeneID; 361527; -.
DR KEGG; rno:361527; -.
DR UCSC; RGD:1308248; rat.
DR CTD; 23646; -.
DR RGD; 1308248; Pld3.
DR eggNOG; KOG3603; Eukaryota.
DR GeneTree; ENSGT00950000183059; -.
DR HOGENOM; CLU_027021_0_0_1; -.
DR InParanoid; Q5FVH2; -.
DR OMA; THFIPNT; -.
DR OrthoDB; 1057467at2759; -.
DR PhylomeDB; Q5FVH2; -.
DR TreeFam; TF313378; -.
DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis.
DR PRO; PR:Q5FVH2; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000018390; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; Q5FVH2; RN.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISO:RGD.
DR GO; GO:0045145; F:single-stranded DNA 5'-3' exodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0014902; P:myotube differentiation; ISS:UniProtKB.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR InterPro; IPR032803; PLDc_3.
DR InterPro; IPR001736; PLipase_D/transphosphatidylase.
DR Pfam; PF00614; PLDc; 1.
DR Pfam; PF13918; PLDc_3; 1.
DR SMART; SM00155; PLDc; 2.
DR PROSITE; PS50035; PLD; 2.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Endosome; Exonuclease; Glycoprotein;
KW Golgi apparatus; Hydrolase; Immunity; Inflammatory response; Lysosome;
KW Membrane; Nuclease; Reference proteome; Repeat; Signal-anchor;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..488
FT /note="5'-3' exonuclease PLD3"
FT /id="PRO_0000280330"
FT TOPO_DOM 1..38
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IV08"
FT TRANSMEM 39..59
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000250|UniProtKB:Q8IV08"
FT TOPO_DOM 60..488
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IV08"
FT DOMAIN 194..221
FT /note="PLD phosphodiesterase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT DOMAIN 409..435
FT /note="PLD phosphodiesterase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 199
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
SQ SEQUENCE 488 AA; 54399 MW; 081AA487F575747A CRC64;
MKPKLMYQEL KVPVEEPAGE LPMNEIEAWK AAEKKARWVL LVLILAVVGF GALMTQLFLW
EYGDLHLFGP NQHPAPCYDP CEAVLVESIP EGLEFPNATT SNPSTSQAWL GLLAGAHSSL
DIASFYWTLT NNDTHTQEPS AQQGEEVLQQ LQALAPRGVK VRIAVSKPNG PLADLQSLLQ
SGAQVRMVDM QKLTHGVLHT KFWVVDQTHF YLGSANMDWR SLTQVKELGV VMYNCSCLAR
DLTKIFEAYW FLGQAGSSIP STWPRPFDTR YNQETPMEIC LNGTPALAYL ASAPPPLCPG
GRTPDLKALL SVVDNARSFI YIAVMNYLPT MEFSHPRRFW PAIDDGLRRA AYERGVKVRL
LISCWGHSEP SMRSFLLSLA ALRDNHTHSD IQVKLFVVPA DEAQARIPYA RVNHNKYMVT
ERTTYIGTSN WSGSYFTETA GTSLLVTQNG HGGLRSQLEA VFLRDWESPY SHNLDTSADS
VGNACRLL
