PLD4
entrez
122618
canonical
uniprot
Q96BZ4
canonical
ensembl
ENSG00000166428
resolver
ensp
ENSP00000376372
resolver
ensp
ENSP00000438677
resolver
ensp
ENSP00000497627
resolver
ensp
ENSP00000532805
resolver
ensp
ENSP00000532806
resolver
enst
ENST00000392593
resolver
enst
ENST00000540372
resolver
enst
ENST00000862746
resolver
enst
ENST00000862747
resolver
genesymbol
PLD4
resolver
genesymbol_syn
C14orf175
resolver
hgnc
HGNC:23792
resolver
uniprot
B4DI07
resolver
uniprot
B4DJQ6
resolver
uniprot
F5H2B5
resolver
uniprot
Q6UWD2
resolver
uniprot_entry
B4DI07_HUMAN
resolver
uniprot_entry
B4DJQ6_HUMAN
resolver
uniprot_entry
F5H2B5_HUMAN
resolver
uniprot_entry
PLD4_HUMAN
resolver
uniprot_sec
Q6UWD2
resolver
activity_regulation
ACTIVITY REGULATION: The exonuclease activity toward ssDNA substrate is Ca(2+) and Mg(2+)-independent, but it is inhibited by Fe(2+), Cu(2+) and to a lesser extent Zn(2+) ions. {ECO:0000269|PubMed:38537643}.
uniprot
proteins
amino_acid_sequence
MLKPLWKAAVAPTWPCSMPPRRPWDREAGTLQVLGALAVLWLGSVALICLLWQVPRPPTWGQVQPKDVPRSWEHGSSPAWEPLEAEARQQRDSCQLVLVESIPQDLPSAAGSPSAQPLGQAWLQLLDTAQESVHVASYYWSLTGPDIGVNDSSSQLGEALLQKLQQLLGRNISLAVATSSPTLARTSTDLQVLAARGAHVRQVPMGRLTRGVLHSKFWVVDGRHIYMGSANMDWRSLTQVKELGAVIYNCSHLAQDLEKTFQTYWVLGVPKAVLPKTWPQNFSSHFNRFQPFHGLFDGVPTTAYFSASPPALCPQGRTRDLEALLAVMGSAQEFIYASVMEYFPTTRFSHPPRYWPVLDNALRAAAFGKGVRVRLLVGCGLNTDPTMFPYLRSLQALSNPAANVSVDVKVFIVPVGNHSNIPFSRVNHSKFMVTEKAAYIGTSNWSEDYFSSTAGVGLVVTQSPGAQPAGATVQEQLRQLFERDWSSRYAVGLDGQAPGQDCVWQG
uniprot
proteins
disease_involvement
DISEASE: Systemic lupus erythematosus 18 (SLEB18) [MIM:621369]: An autosomal recessive form of systemic lupus erythematosus, a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. The disease is marked by a wide range of system dysfunctions, and an elevated erythrocyte sedimentation rate. SLEB18 patients present with a renal phenotype characterized by proliferative lupus nephritis, and with hematological features including leukopenia, anemia and thrombocytopenia. {ECO:0000269|PubMed:40931063}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.1.-
uniprot
proteins
ec_number
3.1.16.1
uniprot
proteins
function
FUNCTION: Lysosomal 5'->3' exonuclease that functions in nucleic-acid sensing by immune cells. Hydrolyzes phosphodiester bond in single-stranded RNA and DNA molecules, with a higher efficiency for molecules with 5' uridine and guanosine residues. It can stall at certain sites and does not necessarily proceed to complete exonucleolytic degradation, thereby producing nucleoside 3'-monophosphates but also 5'-end 5'-hydroxy deoxyribonucleotide/ribonucleotide fragments (PubMed:30111894, PubMed:34620855, PubMed:38537643, PubMed:38697119, PubMed:40931063). Through the processing of self and exogenous RNA and DNA molecules, provides molecular signals to toll-like receptors (TLRs) in innate immunity. Partially redundant with PLD3, it cooperates with the RNase T2/RNASET2 to generate 2',3'-cGMP and cytidine-rich RNA fragments that occupy the two TLR7 ligand-binding pockets, to trigger receptor activation and signaling (PubMed:38697119). Can exert polynucleotide phosphatase activity toward 5'-phosphorylated single-stranded DNA substrates although at a slow rate (PubMed:38537643). Could play a role in phagocytosis of activated microglia (By similarity). {ECO:0000250|UniProtKB:Q8BG07, ECO:0000269|PubMed:30111894, ECO:0000269|PubMed:34620855, ECO:0000269|PubMed:38537643, ECO:0000269|PubMed:38697119, ECO:0000269|PubMed:40931063}.; FUNCTION: Can alternatively catalyze the transfer (transphosphatidylation) of a glycerol group between (S,R)-lysophosphatidylglycerol (LPG) and monoacylglycerol (MAG). The reaction is characterized by an R-to-S stereo-inversion which is essential for the resistance of the produced (S,S)-bis(monoacylglycero)phosphates (BMPs) to lysosomal degradation. The resulting BMPs, are phospholipids required for the formation of lysosomal intralumenal vesicles (ILVs) where lipid degradation can occur. {ECO:0000269|PubMed:39423811}.
uniprot
proteins
mass_dalton
55626
uniprot
proteins
mutagenesis
MUTAGEN 183; /note="L->G: Loss of exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 212; /note="V->A: Loss of exonuclease activity toward ssDNA substrate; when associated with A-348."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 214; /note="H->A: Loss of exonuclease and phosphatase activities toward ssDNA; when associated with A-414. Loss of (S,S)-BMP synthase activity. No effect on protein expression or localization to lysosomes."; /evidence="ECO:0000269|PubMed:38537643, ECO:0000269|PubMed:39423811"; MUTAGEN 216; /note="K->A: Loss of (S,S)-BMP synthase activity. No effect on protein expression or localization to lysosomes."; /evidence="ECO:0000269|PubMed:39423811"; MUTAGEN 221; /note="D->A: Loss of (S,S)-BMP synthase activity. No effect on protein expression or localization to lysosomes. Loss of protein stability; when associated with A-435."; /evidence="ECO:0000269|PubMed:38537643, ECO:0000269|PubMed:39423811"; MUTAGEN 235; /note="R->Q: Tends to form aggregates. Loss of exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 252; /note="H->Q: No effect on exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 255; /note="Q->L: No effect on exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 283; /note="S->L: Tends to form aggregates. Decreases exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 326; /note="A->V: No effect on exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 348; /note="F->A: Loss of exonuclease activity toward ssDNA; when associated with A-212."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 368; /note="G->S: Increases exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643"; MUTAGEN 426; /note="V->A: Loss of (S,S)-BMP synthase activity. No effect on protein expression or localization to lysosomes."; /evidence="ECO:0000269|PubMed:39423811"; MUTAGEN 428; /note="H->A: Loss of exonuclease and phosphatase activities; when associated with A-414. Loss of (S,S)-BMP synthase activity. No effect on protein expression or localization to lysosomes."; /evidence="ECO:0000269|PubMed:38537643, ECO:0000269|PubMed:39423811"; MUTAGEN 435; /note="E->A: Loss of (S,S)-BMP synthase activity. No effect on protein expression or localization to lysosomes. Loss of protein stability; when associated with A-221."; /evidence="ECO:0000269|PubMed:38537643, ECO:0000269|PubMed:39423811"; MUTAGEN 435; /note="E->D: No effect on (S,S)-BMP synthase activity, protein expression or localization to lysosomes."; /evidence="ECO:0000269|PubMed:39423811"; MUTAGEN 497; /note="A->V: No effect on exonuclease activity toward ssDNA substrate."; /evidence="ECO:0000269|PubMed:38537643
uniprot
proteins
post_translational_modification
PTM: Highly N-glycosylated. {ECO:0000250|UniProtKB:Q8BG07}.
uniprot
proteins
protein_family
Phospholipase D family
uniprot
proteins
pubmed
12975309
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
30111894
uniprot
proteins
pubmed
34620855
uniprot
proteins
pubmed
38537643
uniprot
proteins
pubmed
38697119
uniprot
proteins
pubmed
39423811
uniprot
proteins
pubmed
40931063
uniprot
proteins
pubmed
41073790
uniprot
proteins
sequence_length
506
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:39423811}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q8BG07}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q8BG07}. Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q8BG07}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q8BG07}. Nucleus {ECO:0000250|UniProtKB:Q8BG07}. Early endosome {ECO:0000250|UniProtKB:Q8BG07}. Cytoplasmic vesicle, phagosome {ECO:0000250|UniProtKB:Q8BG07}. Note=Activation of microglia induces translocation of PLD4 from the nucleus to the phagosomes. {ECO:0000250|UniProtKB:Q8BG07}.
uniprot
proteins
transmembrane_region
TRANSMEM 31..51; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins