PLD6
entrez
201164
canonical
uniprot
Q8N2A8
canonical
ensembl
ENSG00000179598
resolver
ensp
ENSP00000317177
resolver
enst
ENST00000321560
resolver
genesymbol
PLD6
resolver
hgnc
HGNC:30447
resolver
uniprot
Q8N5Y1
resolver
uniprot_entry
PLD6_HUMAN
resolver
uniprot_sec
Q8N5Y1
resolver
activity_regulation
ACTIVITY REGULATION: MYC stimulates its phospholipase activity (PubMed:26678338). MIGA1 and MIGA2 increase PLD6 self-association affinity and affects the homodimer conformation facilitating its phospholipase activity over the nuclease activity (PubMed:26711011). Single stranded DNA (ssDNA) hydrolase activity does not depend upon, but is stimulated by the presence of Ca(2+) and Mn(2+) (By similarity). {ECO:0000250|UniProtKB:Q5SWZ9, ECO:0000269|PubMed:26678338, ECO:0000269|PubMed:26711011}.
uniprot
proteins
amino_acid_sequence
MGRLSWQVAAAAAVGLALTLEALPWVLRWLRSRRRRPRREALFFPSQVTCTEALLRAPGAELAELPEGCPCGLPHGESALSRLLRALLAARASLDLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFERIWEQFNPTKYTFFPPKKSHGSCAPPVSRAGGRLLSWHRTCGTSSESQT
uniprot
proteins
ec_number
3.1.4.-
uniprot
proteins
function
FUNCTION: Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:21397847, PubMed:28063496). Interaction with Mitoguardin (MIGA1 or MIGA2) affects the dimer conformation, facilitating the lipase activity over the nuclease activity (PubMed:26711011). Plays a key role in mitochondrial fusion and fission via its phospholipase activity (PubMed:17028579, PubMed:24599962, PubMed:26678338). In its phospholipase role, it uses the mitochondrial lipid cardiolipin as substrate to generate phosphatidate (PA or 1,2-diacyl-sn-glycero-3-phosphate), a second messenger signaling lipid (PubMed:17028579, PubMed:26711011). Production of PA facilitates Mitofusin-mediated fusion, whereas the cleavage of PA by the Lipin family of phosphatases produces diacylgycerol (DAG) which promotes mitochondrial fission (PubMed:24599962). Both Lipin and DAG regulate mitochondrial dynamics and membrane fusion/fission, important processes for adapting mitochondrial metabolism to changes in cell physiology. Mitochondrial fusion enables cells to cope with the increased nucleotide demand during DNA synthesis (PubMed:26678338). Mitochondrial function and dynamics are closely associated with biological processes such as cell growth, proliferation, and differentiation (PubMed:21397848). Mediator of MYC activity, promotes mitochondrial fusion and activates AMPK which in turn inhibits YAP/TAZ, thereby inducing cell growth and proliferation (PubMed:26678338). The endonuclease activity plays a critical role in PIWI-interacting RNA (piRNA) biogenesis during spermatogenesis (PubMed:21397847, PubMed:21397848). Implicated in spermatogenesis and sperm fertility in testicular germ cells, its single strand-specific nuclease activity is critical for the biogenesis/maturation of PIWI-interacting RNA (piRNA). MOV10L1 selectively binds to piRNA precursors and funnels them to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins. Cleaves either DNA or RNA substrates with similar affinity, producing a 5' phosphate end, in this way it participates in the processing of primary piRNA transcripts. piRNAs provide essential protection against the activity of mobile genetic elements. piRNA-mediated transposon silencing is thus critical for maintaining genome stability, in particular in germline cells when transposons are mobilized as a consequence of wide-spread genomic demethylation (By similarity). PA may act as signaling molecule in the recognition/transport of the precursor RNAs of primary piRNAs (PubMed:21397847). Interacts with tesmin in testes, suggesting a role in spermatogenesis via association with its interacting partner (By similarity). {ECO:0000250|UniProtKB:Q5SWZ9, ECO:0000269|PubMed:17028579, ECO:0000269|PubMed:21397847, ECO:0000269|PubMed:21397848, ECO:0000269|PubMed:24599962, ECO:0000269|PubMed:26678338, ECO:0000269|PubMed:26711011, ECO:0000269|PubMed:28063496}.
uniprot
proteins
mass_dalton
28273
uniprot
proteins
mutagenesis
MUTAGEN 156; /note="H->N: Mitochondrial fragmentation. No apoptosis, no alterations of cell homeostasis."; /evidence="ECO:0000269|PubMed:17028579, ECO:0000269|PubMed:21397848
uniprot
proteins
protein_family
MitoPLD/Zucchini subfamily
uniprot
proteins
protein_family
Phospholipase D family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17028579
uniprot
proteins
pubmed
21397847
uniprot
proteins
pubmed
21397848
uniprot
proteins
pubmed
24599962
uniprot
proteins
pubmed
26678338
uniprot
proteins
pubmed
26711011
uniprot
proteins
pubmed
28063496
uniprot
proteins
pubmed
28852571
uniprot
proteins
pubmed
38843396
uniprot
proteins
sequence_length
252
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000269|PubMed:17028579}; Single-pass membrane protein {ECO:0000269|PubMed:17028579}. Golgi apparatus {ECO:0000250|UniProtKB:Q5SWZ9}. Note=Localization in the mitochondrial outer membrane is found in different cell types where phospholipase is the predominant activity, however, in pachytene spermatocytes and spermatids of mouse testes where nuclease activity is predominant, localization is restricted to the Golgi, suggesting this enzyme is localized in different subcellular compartments depending on the role (phospholipase or nuclease) it needs to play in each cell type and developmental stage. {ECO:0000305}.
uniprot
proteins
transmembrane_region
TRANSMEM 5..27; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins