PLD6_CANLF
ID PLD6_CANLF Reviewed; 254 AA.
AC E2RD63;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Mitochondrial cardiolipin hydrolase;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q5SWZ9};
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=PLD 6;
GN Name=PLD6;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
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. Mediator of
CC MYC activity, promotes mitochondrial fusion and activates AMPK which in
CC turn inhibits YAP/TAZ, thereby inducing cell growth and proliferation.
CC The endonuclease activity plays a critical role in PIWI-interacting RNA
CC (piRNA) biogenesis during spermatogenesis. Implicated in
CC spermatogenesis and sperm fertility in testicular germ cells, its
CC single strand-specific nuclease activity is critical for the
CC biogenesis/maturation of PIWI-interacting RNA (piRNA). 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. Cleaves either DNA or RNA substrates with similar
CC affinity, producing a 5' phosphate end, in this way it participates in
CC the processing of primary piRNA transcripts. piRNAs provide essential
CC protection against the activity of mobile genetic elements. piRNA-
CC mediated transposon silencing is thus critical for maintaining genome
CC stability, in particular in germline cells when transposons are
CC mobilized as a consequence of wide-spread genomic demethylation. PA may
CC act as signaling molecule in the recognition/transport of the precursor
CC RNAs of primary piRNAs. Interacts with tesmin in testes, suggesting a
CC role in spermatogenesis via association with its interacting partner
CC (By similarity). {ECO:0000250|UniProtKB:Q5SWZ9,
CC ECO:0000250|UniProtKB:Q8N2A8}.
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+) (By similarity). MIGA1 and MIGA2 increase PLD6 self-association
CC affinity and affects the homodimer conformation facilitating its
CC phospholipase activity over the nuclease activity. MYC induces its
CC expression and stimulates its phospholipase activity (By similarity).
CC {ECO:0000250|UniProtKB:Q5SWZ9, ECO:0000250|UniProtKB:Q8N2A8}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with MOV10L1. Interacts
CC with MIGA1 and MIGA2; possibly facilitating homodimer formation (By
CC similarity). Interacts with GK2 (By similarity).
CC {ECO:0000250|UniProtKB:Q5SWZ9, ECO:0000250|UniProtKB:Q8N2A8}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q5SWZ9}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5SWZ9}. Nucleus membrane
CC {ECO:0000250|UniProtKB:Q5SWZ9}. Cell membrane
CC {ECO:0000250|UniProtKB:Q5SWZ9}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q5SWZ9}. 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:0000250|UniProtKB:Q5SWZ9}.
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 -!- 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:0000250|UniProtKB:Q5SWZ9}.
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DR AlphaFoldDB; E2RD63; -.
DR SMR; E2RD63; -.
DR STRING; 9612.ENSCAFP00000027279; -.
DR PaxDb; E2RD63; -.
DR eggNOG; ENOG502RXG9; Eukaryota.
DR HOGENOM; CLU_080814_0_1_1; -.
DR InParanoid; E2RD63; -.
DR OMA; QPFIKEF; -.
DR TreeFam; TF332817; -.
DR Proteomes; UP000002254; Unplaced.
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; ISS: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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043046; P:DNA methylation involved in gamete generation; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051321; P:meiotic cell cycle; ISS:UniProtKB.
DR GO; GO:0008053; P:mitochondrial fusion; ISS:UniProtKB.
DR GO; GO:0030719; P:P granule organization; ISS:UniProtKB.
DR GO; GO:0034587; P:piRNA metabolic process; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; ISS: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 3: Inferred from homology;
KW Cell membrane; Differentiation; Endonuclease; Golgi apparatus; Hydrolase;
KW Lipid degradation; Lipid metabolism; Meiosis; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion outer membrane; Nuclease; Nucleus;
KW Reference proteome; Spermatogenesis; Transmembrane; Transmembrane helix;
KW Zinc; Zinc-finger.
FT CHAIN 1..254
FT /note="Mitochondrial cardiolipin hydrolase"
FT /id="PRO_0000408333"
FT TOPO_DOM 1..9
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 155..182
FT /note="PLD phosphodiesterase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ZN_FING 49..82
FT /note="C3H1-type; atypical"
FT REGION 1..43
FT /note="Required for mitochondrial localization"
FT /evidence="ECO:0000250"
FT ACT_SITE 160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 167
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
SQ SEQUENCE 254 AA; 28565 MW; E93711B801BF883E CRC64;
MERFRWQVAA VAAVGLALAL EALPSVLCWL RAGRRQQQRP PRRQVLFFPS QVTCTEALLQ
APGEAPSGPP AGCRCSLPHG ESSLSRLLRA LLAARASLEL CLFAFSSPQL GRAVQLLHQR
GVRVRVITDC DYMALNGSQI GLLRKAGIQV RHDQDLGYMH HKFAIVDKKV LITGSLNWTT
QAIQNNRENV LIMEDEEYVR LFLEEFERIW EEFNPTKYTF FPQKKTGTSL PPQVSCFGQL
VSCHSKCSHH LSQV
