PLD6_MOUSE
ID PLD6_MOUSE Reviewed; 221 AA.
AC Q5SWZ9; B7ZN71; Q3UTA3; Q8BVM0;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Mitochondrial cardiolipin hydrolase;
DE EC=3.1.-.- {ECO:0000269|PubMed:23064227, ECO:0000269|PubMed:23064230};
DE AltName: Full=Choline phosphatase 6;
DE AltName: Full=Mitochondrial phospholipase {ECO:0000250|UniProtKB:Q8N2A8};
DE Short=MitoPLD {ECO:0000250|UniProtKB:Q8N2A8};
DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q8N2A8};
DE AltName: Full=Phosphatidylcholine-hydrolyzing phospholipase D6;
DE AltName: Full=Phospholipase D6;
DE Short=PLD6 {ECO:0000303|PubMed:33783608};
DE AltName: Full=Protein zucchini homolog {ECO:0000250|UniProtKB:Q9VKD7};
DE Short=mZuc;
GN Name=Pld6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Egg, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-195 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21397847; DOI=10.1016/j.devcel.2011.01.005;
RA Watanabe T., Chuma S., Yamamoto Y., Kuramochi-Miyagawa S., Totoki Y.,
RA Toyoda A., Hoki Y., Fujiyama A., Shibata T., Sado T., Noce T., Nakano T.,
RA Nakatsuji N., Lin H., Sasaki H.;
RT "MITOPLD is a mitochondrial protein essential for nuage formation and piRNA
RT biogenesis in the mouse germline.";
RL Dev. Cell 20:364-375(2011).
RN [6]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=21397848; DOI=10.1016/j.devcel.2011.01.004;
RA Huang H., Gao Q., Peng X., Choi S.Y., Sarma K., Ren H., Morris A.J.,
RA Frohman M.A.;
RT "piRNA-associated germline nuage formation and spermatogenesis require
RT MitoPLD profusogenic mitochondrial-surface lipid signaling.";
RL Dev. Cell 20:376-387(2011).
RN [7]
RP FUNCTION.
RX PubMed=23064230; DOI=10.1038/nature11509;
RA Nishimasu H., Ishizu H., Saito K., Fukuhara S., Kamatani M.K.,
RA Bonnefond L., Matsumoto N., Nishizawa T., Nakanaga K., Aoki J.,
RA Ishitani R., Siomi H., Siomi M.C., Nureki O.;
RT "Structure and function of Zucchini endoribonuclease in piRNA biogenesis.";
RL Nature 491:284-287(2012).
RN [8]
RP FUNCTION, AND INTERACTION WITH MOV10L1.
RX PubMed=25762440; DOI=10.1101/gad.254631.114;
RA Vourekas A., Zheng K., Fu Q., Maragkakis M., Alexiou P., Ma J.,
RA Pillai R.S., Mourelatos Z., Wang P.J.;
RT "The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA
RT processing.";
RL Genes Dev. 29:617-629(2015).
RN [9]
RP FUNCTION.
RX PubMed=26678338; DOI=10.1016/j.ccell.2015.10.013;
RA von Eyss B., Jaenicke L.A., Kortlever R.M., Royla N., Wiese K.E.,
RA Letschert S., McDuffus L.A., Sauer M., Rosenwald A., Evan G.I., Kempa S.,
RA Eilers M.;
RT "A MYC-Driven Change in Mitochondrial Dynamics Limits YAP/TAZ Function in
RT Mammary Epithelial Cells and Breast Cancer.";
RL Cancer Cell 28:743-757(2015).
RN [10]
RP INTERACTION WITH GK2.
RX PubMed=28852571; DOI=10.1038/celldisc.2017.30;
RA Chen Y., Liang P., Huang Y., Li M., Zhang X., Ding C., Feng J., Zhang Z.,
RA Zhang X., Gao Y., Zhang Q., Cao S., Zheng H., Liu D., Songyang Z.,
RA Huang J.;
RT "Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm
RT mitochondrial sheath formation and male fertility.";
RL Cell Discov. 3:17030-17030(2017).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=33783608; DOI=10.1007/s00441-021-03442-7;
RA Riew T.R., Kim S., Jin X., Kim H.L., Hwang W.C., Kang M., Yang E.S.,
RA Lee M.Y., Min D.S.;
RT "Cellular and subcellular localization of endogenous phospholipase D6 in
RT seminiferous tubules of mouse testes.";
RL Cell Tissue Res. 385:191-205(2021).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 31-221, FUNCTION,
RP HOMODIMERIZATION, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-153.
RX PubMed=23064227; DOI=10.1038/nature11502;
RA Ipsaro J.J., Haase A.D., Knott S.R., Joshua-Tor L., Hannon G.J.;
RT "The structural biochemistry of Zucchini implicates it as a nuclease in
RT piRNA biogenesis.";
RL Nature 491:279-283(2012).
CC -!- FUNCTION: Presents phospholipase and nuclease activities, depending on
CC the different physiological conditions. Interaction with Mitoguardin
CC (MIGA1 or MIGA2) affects the dimer conformation, facilitating the
CC lipase activity over the nuclease activity. Plays a key role in
CC mitochondrial fusion and fission via its phospholipase activity. In its
CC phospholipase role, it uses the mitochondrial lipid cardiolipin as
CC substrate to generate phosphatidate (PA or 1,2-diacyl-sn-glycero-3-
CC phosphate), a second messenger signaling lipid. Production of PA
CC facilitates Mitofusin-mediated fusion, whereas the cleavage of PA by
CC the Lipin family of phosphatases produces diacylgycerol (DAG) which
CC promotes mitochondrial fission. Both Lipin and DAG regulate
CC mitochondrial dynamics and membrane fusion/fission, important processes
CC for adapting mitochondrial metabolism to changes in cell physiology.
CC Mitochondrial fusion enables cells to cope with the increased
CC nucleotide demand during DNA synthesis (By similarity). Mitochondrial
CC function and dynamics are closely associated with biological processes
CC such as cell growth, proliferation, and differentiation
CC (PubMed:21397848). Mediator of MYC activity, promotes mitochondrial
CC fusion and activates AMPK which in turn inhibits YAP/TAZ, thereby
CC inducing cell growth and proliferation (PubMed:26678338). The
CC endonuclease activity plays a critical role in PIWI-interacting RNA
CC (piRNA) biogenesis during spermatogenesis (PubMed:21397847,
CC PubMed:21397848). Implicated in spermatogenesis and sperm fertility in
CC testicular germ cells, its single strand-specific nuclease activity is
CC critical for the biogenesis/maturation of PIWI-interacting RNA (piRNA)
CC (PubMed:21397847, PubMed:23064230, PubMed:23064227). MOV10L1
CC selectively binds to piRNA precursors and funnels them to the
CC endonuclease that catalyzes the first cleavage step of piRNA processing
CC to generate piRNA intermediate fragments that are subsequently loaded
CC to Piwi proteins (PubMed:25762440). Cleaves either DNA or RNA
CC substrates with similar affinity, producing a 5' phosphate end, in this
CC way it participates in the processing of primary piRNA transcripts.
CC piRNAs provide essential protection against the activity of mobile
CC genetic elements. piRNA-mediated transposon silencing is thus critical
CC for maintaining genome stability, in particular in germline cells when
CC transposons are mobilized as a consequence of wide-spread genomic
CC demethylation (PubMed:23064230, PubMed:23064227). PA may act as
CC signaling molecule in the recognition/transport of the precursor RNAs
CC of primary piRNAs (PubMed:21397847). Interacts with tesmin in testes,
CC suggesting a role in spermatogenesis via association with its
CC interacting partner (PubMed:33783608). {ECO:0000250|UniProtKB:Q8N2A8,
CC ECO:0000269|PubMed:21397847, ECO:0000269|PubMed:21397848,
CC ECO:0000269|PubMed:23064227, ECO:0000269|PubMed:23064230,
CC ECO:0000269|PubMed:25762440, ECO:0000269|PubMed:26678338,
CC ECO:0000269|PubMed:33783608}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cardiolipin + H2O = 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-
CC glycerol) + a 1,2-diacyl-sn-glycero-3-phosphate + H(+);
CC Xref=Rhea:RHEA:44884, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58608, ChEBI:CHEBI:62237, ChEBI:CHEBI:64716;
CC Evidence={ECO:0000250|UniProtKB:Q8N2A8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44885;
CC Evidence={ECO:0000250|UniProtKB:Q8N2A8};
CC -!- ACTIVITY REGULATION: Single stranded DNA (ssDNA) hydrolase activity
CC does not depend upon, but is stimulated by the presence of Ca(2+) and
CC Mn(2+) (PubMed:23064227). MIGA1 and MIGA2 increase PLD6 self-
CC association affinity and affects the homodimer conformation
CC facilitating its phospholipase activity over the nuclease activity. MYC
CC induces its expression and stimulates its phospholipase activity (By
CC similarity). {ECO:0000250|UniProtKB:Q8N2A8,
CC ECO:0000269|PubMed:23064227}.
CC -!- SUBUNIT: Homodimer (PubMed:23064227). Interacts with MOV10L1
CC (PubMed:25762440). Interacts with MIGA1 and MIGA2; possibly
CC facilitating homodimer formation (By similarity). Interacts with GK2
CC (PubMed:28852571). {ECO:0000250|UniProtKB:Q8N2A8,
CC ECO:0000269|PubMed:23064227, ECO:0000269|PubMed:25762440,
CC ECO:0000269|PubMed:28852571, ECO:0000269|PubMed:33783608}.
CC -!- INTERACTION:
CC Q5SWZ9-1; Q5SWZ9-1: Pld6; NbExp=3; IntAct=EBI-16017309, EBI-16017309;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:21397847}; Single-pass membrane protein
CC {ECO:0000269|PubMed:21397847}. Nucleus membrane
CC {ECO:0000269|PubMed:21397847}. Cell membrane
CC {ECO:0000269|PubMed:21397847}. Golgi apparatus
CC {ECO:0000269|PubMed:33783608}. Note=Localization in the mitochondrial
CC outer membrane is found in different cell types where phospholipase was
CC the predominant activity, however, in pachytene spermatocytes and
CC spermatids of mouse testes where nuclease activity is predominant,
CC localization is restricted to the Golgi, suggesting this enzyme is
CC localized in different subcellular compartments depending on the role
CC (phospholipase or nuclease) it needs to play in each cell type and
CC developmental stage. {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5SWZ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5SWZ9-2; Sequence=VSP_032474, VSP_032475;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in testis (at protein
CC level) and in growing ovary (PubMed:21397847, PubMed:33783608). Also
CC expressed in the brain, eye and urinary bladder (at protein level), but
CC its levels were low or undetectable in other organs (PubMed:33783608).
CC {ECO:0000269|PubMed:21397847, ECO:0000269|PubMed:33783608}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic testis at 16.5 dpc (at
CC protein level). Expressed at low levels in type A and B spermatogonia,
CC increases 5-fold in spermatocytes undergoing meiosis (pachytene
CC spermatocytes), and then decreases again in round spermatids. Expressed
CC at low levels in testes in young mice, peaks from postnatal day 14 to
CC day 29 with the onset of puberty andpersists in adulthood (at protein
CC level). {ECO:0000269|PubMed:21397847, ECO:0000269|PubMed:21397848}.
CC -!- DOMAIN: In contrast to other members of the phospholipase D family,
CC contains only one PLD phosphodiesterase domain, suggesting that it has
CC a single half-catalytic and requires homodimerization to form a
CC complete active site. {ECO:0000250|UniProtKB:Q8N2A8}.
CC -!- DISRUPTION PHENOTYPE: Males are sterile, because of meiotic arrest
CC during spermatogenesis due to demethylation and subsequent derepression
CC of transposable elements. No spermatids were observed in the mutant
CC testes, and no spermatozoon in the epididymis. Effects are caused by
CC defects in primary piRNA biogenesis: in contrast to wild-type cells
CC neither mitochondria nor associated meiotic nuage (named P granule) are
CC aggregated. {ECO:0000269|PubMed:21397847, ECO:0000269|PubMed:21397848}.
CC -!- SIMILARITY: Belongs to the phospholipase D family. MitoPLD/Zucchini
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Evidence for subcellular location in the Golgi was determined
CC in pachytene spermatocytes and spermatids in mouse testes. They observe
CC that the ectopically expressed PLD6 protein was localized to the
CC mitochondria in PLD6-transfected cells. Authors claim a possible
CC explanation for the contradictory results is that previous studies have
CC reported the localization of exogenous PLD6, but not endogenous PLD6,
CC in cultured cells. The reason for differences observed in subcellular
CC localization of exogenous and endogenous PLD6 is not clear but one
CC attributable reason may be that different types of anti-PLD6 antibodies
CC have been used in previous studies. {ECO:0000269|PubMed:33783608}.
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DR EMBL; AK077214; BAC36687.1; -; mRNA.
DR EMBL; AK139586; BAE24077.1; -; mRNA.
DR EMBL; AL596204; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC119245; AAI19246.1; -; mRNA.
DR EMBL; BC145052; AAI45053.1; -; mRNA.
DR CCDS; CCDS70199.1; -. [Q5SWZ9-1]
DR RefSeq; NP_001277212.1; NM_001290283.1. [Q5SWZ9-1]
DR RefSeq; NP_898962.2; NM_183139.2. [Q5SWZ9-2]
DR PDB; 4GGJ; X-ray; 1.75 A; A=31-221.
DR PDB; 4GGK; X-ray; 2.10 A; A=31-221.
DR PDBsum; 4GGJ; -.
DR PDBsum; 4GGK; -.
DR AlphaFoldDB; Q5SWZ9; -.
DR SMR; Q5SWZ9; -.
DR BioGRID; 228810; 1.
DR DIP; DIP-59982N; -.
DR STRING; 10090.ENSMUSP00000115503; -.
DR PhosphoSitePlus; Q5SWZ9; -.
DR PaxDb; Q5SWZ9; -.
DR PRIDE; Q5SWZ9; -.
DR ProteomicsDB; 289759; -. [Q5SWZ9-1]
DR ProteomicsDB; 289760; -. [Q5SWZ9-2]
DR Antibodypedia; 63312; 92 antibodies from 21 providers.
DR Ensembl; ENSMUST00000125307; ENSMUSP00000115503; ENSMUSG00000043648. [Q5SWZ9-1]
DR GeneID; 194908; -.
DR KEGG; mmu:194908; -.
DR UCSC; uc007jev.1; mouse. [Q5SWZ9-2]
DR UCSC; uc011xvp.1; mouse. [Q5SWZ9-1]
DR CTD; 201164; -.
DR MGI; MGI:2687283; Pld6.
DR VEuPathDB; HostDB:ENSMUSG00000043648; -.
DR eggNOG; ENOG502RXG9; Eukaryota.
DR GeneTree; ENSGT00390000004368; -.
DR HOGENOM; CLU_080814_0_1_1; -.
DR InParanoid; Q5SWZ9; -.
DR OMA; QPFIKEF; -.
DR OrthoDB; 1489926at2759; -.
DR PhylomeDB; Q5SWZ9; -.
DR TreeFam; TF332817; -.
DR Reactome; R-MMU-1483166; Synthesis of PA.
DR BioGRID-ORCS; 194908; 2 hits in 70 CRISPR screens.
DR PRO; PR:Q5SWZ9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5SWZ9; protein.
DR Bgee; ENSMUSG00000043648; Expressed in spermatocyte and 62 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035755; F:cardiolipin hydrolase activity; ISS:UniProtKB.
DR GO; GO:0016891; F:endoribonuclease activity, producing 5'-phosphomonoesters; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004630; F:phospholipase D activity; TAS:Reactome.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; IMP:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051321; P:meiotic cell cycle; IMP:UniProtKB.
DR GO; GO:0008053; P:mitochondrial fusion; ISS:UniProtKB.
DR GO; GO:0030719; P:P granule organization; IMP:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; IMP:UniProtKB.
DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; ISO:MGI.
DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB.
DR InterPro; IPR025202; PLD-like_dom.
DR InterPro; IPR001736; PLipase_D/transphosphatidylase.
DR Pfam; PF13091; PLDc_2; 1.
DR SMART; SM00155; PLDc; 1.
DR PROSITE; PS50035; PLD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Differentiation;
KW Endonuclease; Golgi apparatus; Hydrolase; Lipid degradation;
KW Lipid metabolism; Meiosis; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion outer membrane; Nuclease; Nucleus; Reference proteome;
KW Spermatogenesis; Transmembrane; Transmembrane helix; Zinc; Zinc-finger.
FT CHAIN 1..221
FT /note="Mitochondrial cardiolipin hydrolase"
FT /id="PRO_0000325911"
FT TOPO_DOM 1..4
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 148..175
FT /note="PLD phosphodiesterase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ZN_FING 44..75
FT /note="C3H1-type; atypical"
FT REGION 1..38
FT /note="Required for mitochondrial localization"
FT ACT_SITE 153
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT VAR_SEQ 139..147
FT /note="AGIQVRHDQ -> GYRYGTTRT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_032474"
FT VAR_SEQ 148..221
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_032475"
FT MUTAGEN 153
FT /note="H->N: Loss of nuclease activity."
FT /evidence="ECO:0000269|PubMed:23064227"
FT STRAND 38..44
FT /evidence="ECO:0007829|PDB:4GGJ"
FT TURN 51..55
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:4GGK"
FT HELIX 76..85
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 88..96
FT /evidence="ECO:0007829|PDB:4GGJ"
FT HELIX 101..112
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:4GGJ"
FT HELIX 132..138
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:4GGJ"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 163..168
FT /evidence="ECO:0007829|PDB:4GGJ"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:4GGJ"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:4GGJ"
FT HELIX 189..205
FT /evidence="ECO:0007829|PDB:4GGJ"
SQ SEQUENCE 221 AA; 25041 MW; A7A2E813281B924E CRC64;
MGRSSWRLVF AAGAGLALAL EALPWLMRWL LAGRRPRREV LFFPSQVTCT EALLQAPGLP
PGPSGCPCSL PHSESSLSRL LRALLAARSS LELCLFAFSS PQLGRAVQLL HQRGVRVRVI
TDCDYMALNG SQIGLLRKAG IQVRHDQDLG YMHHKFAIVD KKVLITGSLN WTTQAIQNNR
ENVLIMEDTE YVRLFLEEFE RIWEEFDPTK YSFFPQKHRG H
