PLD3_MACFA
ID PLD3_MACFA Reviewed; 490 AA.
AC Q4R583;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 61.
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; ORFNames=QccE-15167;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB169661; BAE01742.1; -; mRNA.
DR AlphaFoldDB; Q4R583; -.
DR SMR; Q4R583; -.
DR STRING; 9541.XP_005589317.1; -.
DR PRIDE; Q4R583; -.
DR eggNOG; KOG3603; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
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: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 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 2: Evidence at transcript 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..490
FT /note="5'-3' exonuclease PLD3"
FT /id="PRO_0000280327"
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..490
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8IV08"
FT DOMAIN 196..223
FT /note="PLD phosphodiesterase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT DOMAIN 411..437
FT /note="PLD phosphodiesterase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 203
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 490 AA; 54852 MW; ED2891E1920AB9DF CRC64;
MKPKLMYQEL KVPAEEPANE LPMNEIEAWK AAEKKARWVL LVLILAVVGF GALMTQLFLW
EYGDLHLFGP NQRPAPCYDP CEAVLVESIP EGLDFPNAST GNPSTSQAWL GLLAGAHSSL
DIASFYWTLT NNDTHTQEPS AQQGEEVLRQ LQTLAPKGVN VRIAVSKPNG PQPQTDLQAL
LQSGAQVRMV DMQKLTHGVL HTKFWVVDQT HFYLGSANMD WRSLTQVKEL GVVMYNCSCL
ARDLTKIFEA YWFLGQAGSS IPSTWPRFYD TRYNQETPME ICLNGTPALA YLASAPPPLC
PSGRTPDLKA LLNVVDNARS FIYIAVMNYL PTLEFSHPHR FWPAIDDGLR RAAYERGVKV
RLLVSCWRHS ESSMRAFLLS LAALRDNHTH SDIQVKLFVV PADEAQARIP YARVNHNKYM
VTERATYIGT SNWSGNYFTE TAGTSLLVMQ NGRGSLRSQL EAIFLRDWDS PYSHDLDASA
DSVGNACRLL
