| IED ID | IndEnz0005000906 |
| Enzyme Type ID | lipase000906 |
| Protein Name |
Mitochondrial cardiolipin hydrolase EC 3.1.-.- Choline phosphatase 6 Mitochondrial phospholipase MitoPLD EC 3.1.4.- Phosphatidylcholine-hydrolyzing phospholipase D6 Phospholipase D6 PLD6 Protein zucchini homolog |
| Gene Name | PLD6 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGRLSWQVAAAAAVGLALTLEALPWVLRWLRSRRRRPRREALFFPSQVTCTEALLRAPGAELAELPEGCPCGLPHGESALSRLLRALLAARASLDLCLFAFSSPQLGRAVQLLHQRGVRVRVVTDCDYMALNGSQIGLLRKAGIQVRHDQDPGYMHHKFAIVDKRVLITGSLNWTTQAIQNNRENVLITEDDEYVRLFLEEFERIWEQFNPTKYTFFPPKKSHGSCAPPVSRAGGRLLSWHRTCGTSSESQT |
| Enzyme Length | 252 |
| Uniprot Accession Number | Q8N2A8 |
| Absorption | |
| Active Site | ACT_SITE 156; /evidence=ECO:0000305; ACT_SITE 158; /evidence=ECO:0000255|PROSITE-ProRule:PRU00153; ACT_SITE 163; /evidence=ECO:0000255|PROSITE-ProRule:PRU00153 |
| 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}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a cardiolipin + H2O = 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) + a 1,2-diacyl-sn-glycero-3-phosphate + H(+); Xref=Rhea:RHEA:44884, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58608, ChEBI:CHEBI:62237, ChEBI:CHEBI:64716; Evidence={ECO:0000269|PubMed:17028579, ECO:0000269|PubMed:24599962, ECO:0000269|PubMed:26711011};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44885; Evidence={ECO:0000269|PubMed:17028579, ECO:0000269|PubMed:24599962, ECO:0000269|PubMed:26711011}; |
| DNA Binding | |
| EC Number | 3.1.-.-; 3.1.4.- |
| Enzyme Function | FUNCTION: Presents phospholipase and nuclease activities, depending on the different physiological conditions (PubMed:17028579, PubMed:24599962, 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:24599962, 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}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Domain (1); Mutagenesis (1); Natural variant (2); Region (1); Topological domain (2); Transmembrane (1); Zinc finger (1) |
| Keywords | Differentiation;Endonuclease;Golgi apparatus;Hydrolase;Lipid degradation;Lipid metabolism;Meiosis;Membrane;Metal-binding;Mitochondrion;Mitochondrion outer membrane;Nuclease;Reference proteome;Spermatogenesis;Transmembrane;Transmembrane helix;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| 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}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 14573790; 14654225; 22281006; 23064227; 23064230; 23980886; 8530346; 9140189; 9761774; |
| Motif | |
| Gene Encoded By | |
| Mass | 28,273 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:44884; RHEA:44885 |
| Cross Reference Brenda |