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Q5SWZ9

- PLD6_MOUSE

UniProt

Q5SWZ9 - PLD6_MOUSE

Protein

Mitochondrial cardiolipin hydrolase

Gene

Pld6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 82 (01 Oct 2014)
      Sequence version 1 (21 Dec 2004)
      Previous versions | rss
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    Functioni

    Regulates mitochondrial shape through facilitating mitochondrial fusion. During spermatogenesis, plays a critical role in PIWI-interacting RNA (piRNA) biogenesis. 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. Has been proposed to act as a cardiolipin hydrolase to generate phosphatidic acid at mitochondrial surface (PubMed:21397848). Although it cannot be excluded that it can act as a phospholipase in some circumstances, it should be noted that cardiolipin hydrolase activity is either undetectable in vitro (PubMed:23064227 and PubMed:23064230), or very low. In addition, cardiolipin is almost exclusively found on the inner mitochondrial membrane, while PLD6 localizes to the outer mitochondrial membrane, facing the cytosol. Has been shown to be a backbone-non-specific, single strand-specific nuclease, cleaving either RNA or DNA substrates with similar affinity (PubMed:23064227 and PubMed:23064230). Produces 5' phosphate and 3' hydroxyl termini, suggesting it could directly participate in the processing of primary piRNA transcripts.4 Publications

    Enzyme regulationi

    SsDNA hydrolase activity does not depend upon, but it stimulated by, the presence of Ca2+ and Mn2+.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei153 – 1531PROSITE-ProRule annotation
    Active sitei155 – 1551PROSITE-ProRule annotation
    Active sitei160 – 1601PROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri44 – 7532C3H1-type; atypicalAdd
    BLAST

    GO - Molecular functioni

    1. cardiolipin hydrolase activity Source: UniProtKB
    2. endonuclease activity Source: UniProtKB-KW
    3. metal ion binding Source: UniProtKB-KW
    4. protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    1. DNA methylation involved in gamete generation Source: UniProtKB
    2. lipid catabolic process Source: UniProtKB-KW
    3. meiotic nuclear division Source: UniProtKB
    4. mitochondrial fusion Source: UniProtKB
    5. P granule organization Source: UniProtKB
    6. piRNA metabolic process Source: UniProtKB
    7. spermatid development Source: UniProtKB

    Keywords - Molecular functioni

    Endonuclease, Hydrolase, Nuclease

    Keywords - Biological processi

    Differentiation, Lipid degradation, Lipid metabolism, Meiosis, Spermatogenesis

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_199032. Synthesis of PG.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitochondrial cardiolipin hydrolase (EC:3.1.-.-)
    Alternative name(s):
    Choline phosphatase 6
    Mitochondrial phospholipase
    Short name:
    MitoPLD
    Phosphatidylcholine-hydrolyzing phospholipase D6
    Phospholipase D6
    Short name:
    PLD 6
    Protein zucchini homolog
    Short name:
    mZuc
    Gene namesi
    Name:Pld6
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:2687283. Pld6.

    Subcellular locationi

    Mitochondrion outer membrane 1 Publication; Single-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome
    2. integral component of membrane Source: UniProtKB-KW
    3. mitochondrial outer membrane Source: UniProtKB

    Keywords - Cellular componenti

    Membrane, Mitochondrion, Mitochondrion outer membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mutant animals are born at the expected Mendelian ratio. Females show no discernible phenotype and are fertile. Males are sterile, because of meiotic arrest during spermatogenesis due to demethylation and subsequent derepression of transposable elements. Effects are caused by defects in primary piRNA biogenesis: in contrast to wild-type cells neither mitochondria nor associated meiotic nuage (named P granule) are aggregated.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi153 – 1531H → N: Loss of nuclease activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 221221Mitochondrial cardiolipin hydrolasePRO_0000325911Add
    BLAST

    Proteomic databases

    PaxDbiQ5SWZ9.
    PRIDEiQ5SWZ9.

    PTM databases

    PhosphoSiteiQ5SWZ9.

    Expressioni

    Tissue specificityi

    Predominantly expressed in testis (at protein level). Also expressed at high levels in growing ovary.1 Publication

    Developmental stagei

    Expressed in embryonic testis at 16.5 dpc (at protein level). Expressed at low levels in type A and B spermatogonia, increases 5-fold in spermatocytes undergoing meiosis (pachytene spermatocytes), and then decreases again in round spermatids. Expressed at low levels in testes in young mice, peaks from postnatal day 14 to day 29 with the onset of puberty andpersists in adulthood (at protein level).2 Publications

    Gene expression databases

    BgeeiQ5SWZ9.
    GenevestigatoriQ5SWZ9.

    Interactioni

    Subunit structurei

    Homodimer.

    Protein-protein interaction databases

    DIPiDIP-59982N.
    STRINGi10090.ENSMUSP00000115503.

    Structurei

    Secondary structure

    1
    221
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi38 – 447
    Turni51 – 555
    Beta strandi68 – 703
    Helixi76 – 8510
    Beta strandi88 – 969
    Helixi101 – 11212
    Beta strandi116 – 1238
    Helixi132 – 1387
    Beta strandi142 – 1454
    Beta strandi148 – 1503
    Beta strandi155 – 1595
    Turni160 – 1623
    Beta strandi163 – 1686
    Helixi173 – 1786
    Beta strandi181 – 1866
    Helixi189 – 20517

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4GGJX-ray1.75A31-221[»]
    4GGKX-ray2.10A31-221[»]
    ProteinModelPortaliQ5SWZ9.
    SMRiQ5SWZ9. Positions 35-209.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 44Mitochondrial intermembraneSequence Analysis
    Topological domaini28 – 221194CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei5 – 2723HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini148 – 17528PLD phosphodiesterasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 3838Required for mitochondrial localizationAdd
    BLAST

    Domaini

    In contrast to other members of the phospholipase D family, contains only one PLD phosphodiesterase domain, suggesting that it has a single half-catalytic and requires homodimerization to form a complete active site.By similarity

    Sequence similaritiesi

    Contains 1 C3H1-type zinc finger.Curated
    Contains 1 PLD phosphodiesterase domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri44 – 7532C3H1-type; atypicalAdd
    BLAST

    Keywords - Domaini

    Transmembrane, Transmembrane helix, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG1502.
    GeneTreeiENSGT00390000004368.
    HOGENOMiHOG000082679.
    HOVERGENiHBG108267.
    InParanoidiQ5SWZ9.
    KOiK16862.
    OMAiFPSQVTC.
    OrthoDBiEOG7CNZHW.
    PhylomeDBiQ5SWZ9.
    TreeFamiTF332817.

    Family and domain databases

    InterProiIPR025202. PLD-like_dom.
    IPR001736. PLipase_D/transphosphatidylase.
    [Graphical view]
    PfamiPF13091. PLDc_2. 1 hit.
    [Graphical view]
    SMARTiSM00155. PLDc. 1 hit.
    [Graphical view]
    PROSITEiPS50035. PLD. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q5SWZ9-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGRSSWRLVF AAGAGLALAL EALPWLMRWL LAGRRPRREV LFFPSQVTCT    50
    EALLQAPGLP PGPSGCPCSL PHSESSLSRL LRALLAARSS LELCLFAFSS 100
    PQLGRAVQLL HQRGVRVRVI TDCDYMALNG SQIGLLRKAG IQVRHDQDLG 150
    YMHHKFAIVD KKVLITGSLN WTTQAIQNNR ENVLIMEDTE YVRLFLEEFE 200
    RIWEEFDPTK YSFFPQKHRG H 221
    Length:221
    Mass (Da):25,041
    Last modified:December 21, 2004 - v1
    Checksum:iA7A2E813281B924E
    GO
    Isoform 2 (identifier: Q5SWZ9-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         139-147: AGIQVRHDQ → GYRYGTTRT
         148-221: Missing.

    Show »
    Length:147
    Mass (Da):16,108
    Checksum:iC89BFBDAE7BA570D
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei139 – 1479AGIQVRHDQ → GYRYGTTRT in isoform 2. 2 PublicationsVSP_032474
    Alternative sequencei148 – 22174Missing in isoform 2. 2 PublicationsVSP_032475Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK077214 mRNA. Translation: BAC36687.1.
    AK139586 mRNA. Translation: BAE24077.1.
    AL596204 Genomic DNA. Translation: CAI24298.1.
    BC119245 mRNA. Translation: AAI19246.1.
    BC145052 mRNA. Translation: AAI45053.1.
    CCDSiCCDS70199.1. [Q5SWZ9-1]
    RefSeqiNP_001277212.1. NM_001290283.1. [Q5SWZ9-1]
    NP_898962.2. NM_183139.2. [Q5SWZ9-2]
    UniGeneiMm.344651.

    Genome annotation databases

    EnsembliENSMUST00000125307; ENSMUSP00000115503; ENSMUSG00000043648. [Q5SWZ9-1]
    GeneIDi194908.
    KEGGimmu:194908.
    UCSCiuc007jev.1. mouse. [Q5SWZ9-2]
    uc011xvp.1. mouse. [Q5SWZ9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK077214 mRNA. Translation: BAC36687.1 .
    AK139586 mRNA. Translation: BAE24077.1 .
    AL596204 Genomic DNA. Translation: CAI24298.1 .
    BC119245 mRNA. Translation: AAI19246.1 .
    BC145052 mRNA. Translation: AAI45053.1 .
    CCDSi CCDS70199.1. [Q5SWZ9-1 ]
    RefSeqi NP_001277212.1. NM_001290283.1. [Q5SWZ9-1 ]
    NP_898962.2. NM_183139.2. [Q5SWZ9-2 ]
    UniGenei Mm.344651.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4GGJ X-ray 1.75 A 31-221 [» ]
    4GGK X-ray 2.10 A 31-221 [» ]
    ProteinModelPortali Q5SWZ9.
    SMRi Q5SWZ9. Positions 35-209.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-59982N.
    STRINGi 10090.ENSMUSP00000115503.

    PTM databases

    PhosphoSitei Q5SWZ9.

    Proteomic databases

    PaxDbi Q5SWZ9.
    PRIDEi Q5SWZ9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000125307 ; ENSMUSP00000115503 ; ENSMUSG00000043648 . [Q5SWZ9-1 ]
    GeneIDi 194908.
    KEGGi mmu:194908.
    UCSCi uc007jev.1. mouse. [Q5SWZ9-2 ]
    uc011xvp.1. mouse. [Q5SWZ9-1 ]

    Organism-specific databases

    CTDi 201164.
    MGIi MGI:2687283. Pld6.

    Phylogenomic databases

    eggNOGi COG1502.
    GeneTreei ENSGT00390000004368.
    HOGENOMi HOG000082679.
    HOVERGENi HBG108267.
    InParanoidi Q5SWZ9.
    KOi K16862.
    OMAi FPSQVTC.
    OrthoDBi EOG7CNZHW.
    PhylomeDBi Q5SWZ9.
    TreeFami TF332817.

    Enzyme and pathway databases

    Reactomei REACT_199032. Synthesis of PG.

    Miscellaneous databases

    NextBioi 371672.
    PROi Q5SWZ9.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q5SWZ9.
    Genevestigatori Q5SWZ9.

    Family and domain databases

    InterProi IPR025202. PLD-like_dom.
    IPR001736. PLipase_D/transphosphatidylase.
    [Graphical view ]
    Pfami PF13091. PLDc_2. 1 hit.
    [Graphical view ]
    SMARTi SM00155. PLDc. 1 hit.
    [Graphical view ]
    PROSITEi PS50035. PLD. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Strain: C57BL/6J.
      Tissue: Egg and Testis.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-195 (ISOFORM 1).
      Tissue: Brain.
    4. "MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline."
      Watanabe T., Chuma S., Yamamoto Y., Kuramochi-Miyagawa S., Totoki Y., Toyoda A., Hoki Y., Fujiyama A., Shibata T., Sado T., Noce T., Nakano T., Nakatsuji N., Lin H., Sasaki H.
      Dev. Cell 20:364-375(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    5. "piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling."
      Huang H., Gao Q., Peng X., Choi S.Y., Sarma K., Ren H., Morris A.J., Frohman M.A.
      Dev. Cell 20:376-387(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
    6. Cited for: FUNCTION AS A NUCLEASE, LACK OF CARDIOLIPIN HYDROLASE ACTIVITY.
    7. "The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis."
      Ipsaro J.J., Haase A.D., Knott S.R., Joshua-Tor L., Hannon G.J.
      Nature 491:279-283(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 31-221, FUNCTION AS A NUCLEASE, LACK OF CARDIOLIPIN HYDROLASE ACTIVITY, HOMODIMERIZATION, ENZYME REGULATION, MUTAGENESIS OF HIS-153.

    Entry informationi

    Entry nameiPLD6_MOUSE
    AccessioniPrimary (citable) accession number: Q5SWZ9
    Secondary accession number(s): B7ZN71, Q3UTA3, Q8BVM0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 18, 2008
    Last sequence update: December 21, 2004
    Last modified: October 1, 2014
    This is version 82 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3