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 27-MAR-2024, entry version 133. DE RecName: Full=Mitochondrial cardiolipin hydrolase; DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q8N2A8}; DE AltName: Full=Choline phosphatase 6; DE AltName: Full=Mitochondrial phospholipase {ECO:0000250|UniProtKB:Q8N2A8}; DE Short=MitoPLD {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:0000303|PubMed:23064230}; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SwissPalm; Q5SWZ9; -. DR PaxDb; 10090-ENSMUSP00000115503; -. DR ProteomicsDB; 289759; -. [Q5SWZ9-1] DR ProteomicsDB; 289760; -. [Q5SWZ9-2] DR Antibodypedia; 63312; 97 antibodies from 22 providers. DR Ensembl; ENSMUST00000125307.2; ENSMUSP00000115503.2; ENSMUSG00000043648.8. [Q5SWZ9-1] DR GeneID; 194908; -. DR KEGG; mmu:194908; -. DR UCSC; uc007jev.1; mouse. [Q5SWZ9-2] DR UCSC; uc011xvp.1; mouse. [Q5SWZ9-1] DR AGR; MGI:2687283; -. 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; RIWEEFD; -. DR OrthoDB; 1356899at2759; -. DR PhylomeDB; Q5SWZ9; -. DR TreeFam; TF332817; -. DR Reactome; R-MMU-1483166; Synthesis of PA. DR BioGRID-ORCS; 194908; 2 hits in 75 CRISPR screens. DR PRO; PR:Q5SWZ9; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; Q5SWZ9; Protein. DR Bgee; ENSMUSG00000043648; Expressed in spermatocyte and 65 other cell types or tissues. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. 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: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:0016891; F:RNA endonuclease activity, producing 5'-phosphomonoesters; IBA:GO_Central. 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 processing; IMP:UniProtKB. DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; ISO:MGI. DR GO; GO:0007286; P:spermatid development; IMP:UniProtKB. DR CDD; cd09171; PLDc_vPLD6_like; 1. DR Gene3D; 3.30.870.10; Endonuclease Chain A; 1. DR InterPro; IPR025202; PLD-like_dom. DR InterPro; IPR001736; PLipase_D/transphosphatidylase. DR PANTHER; PTHR43856; CARDIOLIPIN HYDROLASE; 1. DR PANTHER; PTHR43856:SF1; MITOCHONDRIAL CARDIOLIPIN HYDROLASE; 1. DR Pfam; PF13091; PLDc_2; 1. DR SMART; SM00155; PLDc; 1. DR SUPFAM; SSF56024; Phospholipase D/nuclease; 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 //