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Q5SWZ9

- PLD6_MOUSE

UniProt

Q5SWZ9 - PLD6_MOUSE

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Protein

Mitochondrial cardiolipin hydrolase

Gene

Pld6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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
Complete GO annotation...

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 44Mitochondrial intermembraneSequence Analysis
Transmembranei5 – 2723HelicalSequence AnalysisAdd
BLAST
Topological domaini28 – 221194CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

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 – 447Combined sources
Turni51 – 555Combined sources
Beta strandi68 – 703Combined sources
Helixi76 – 8510Combined sources
Beta strandi88 – 969Combined sources
Helixi101 – 11212Combined sources
Beta strandi116 – 1238Combined sources
Helixi132 – 1387Combined sources
Beta strandi142 – 1454Combined sources
Beta strandi148 – 1503Combined sources
Beta strandi155 – 1595Combined sources
Turni160 – 1623Combined sources
Beta strandi163 – 1686Combined sources
Helixi173 – 1786Combined sources
Beta strandi181 – 1866Combined sources
Helixi189 – 20517Combined sources

3D structure databases

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

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

        10         20         30         40         50
MGRSSWRLVF AAGAGLALAL EALPWLMRWL LAGRRPRREV LFFPSQVTCT
60 70 80 90 100
EALLQAPGLP PGPSGCPCSL PHSESSLSRL LRALLAARSS LELCLFAFSS
110 120 130 140 150
PQLGRAVQLL HQRGVRVRVI TDCDYMALNG SQIGLLRKAG IQVRHDQDLG
160 170 180 190 200
YMHHKFAIVD KKVLITGSLN WTTQAIQNNR ENVLIMEDTE YVRLFLEEFE
210 220
RIWEEFDPTK YSFFPQKHRG H
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 83 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