DegronMD - Q8N2A8(PLD6)

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}. View more >>

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GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P211S	TCGA-29-1764	OV	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation altering degron motif	0.5641
p.P211S	DO28364	OV	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation altering degron motif	0.5641
p.P219S	TCGA-A2-A1FZ	BRCA	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.3056
p.P219S	DO2770	BRCA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.3056
p.F216L	TCGA-AP-A05N	UCEC	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation altering degron motif	0.587
p.F216L	DO40851	UCEC	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation altering degron motif	0.587
p.R204H	TCGA-B7-A5TI	STAD	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1667
p.R204H	TCGA-FI-A2D5	UCEC	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1667
p.R204H	DO222328	STAD	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1667
p.R204H	DO41331	UCEC	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1667
p.P228Q	TCGA-CN-6010	HNSC	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.0556
p.P228Q	DO14766	HNSC	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.0556
p.P228Q	DO228948	LICA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.0556
p.K220N	TCGA-EI-6917	READ	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.2778
p.K220N	DO36881	READ	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.2778
p.F217S	TCGA-EO-A3AY	UCEC	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation altering degron motif	0.6871
p.F217S	DO43202	UCEC	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation altering degron motif	0.6871
p.E201Q	TCGA-FD-A6TC	BLCA	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.0833
p.E201Q	TCGA-MA-AA41	CESC	TCGA	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.0833
p.E201Q	DO49755	BLCA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.0833
p.E201Q	DO219723	CESC	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.0833
p.E203D	DO52598	BOCA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1389
p.R204S	DO229028	LICA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1667
p.P211T	DO229008	LICA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation altering degron motif	0.5919
p.G224E	DO229459	SKCA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1667
p.G224R	DO229459	SKCA	ICGC	NPTKYTFFP	CBL_PTK	210:218	Mutation rewiring degron network	0.1667

Kaplan plot for PLD6 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PLD6

UniProt ID: Q8N2A8

Entrez ID: 201164

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)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PLD6 in