Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q5SWZ9 (PLD6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 77. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Pld6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length221 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 (Ref.5). 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 (Ref.7 and Ref.6), 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 (Ref.7 and Ref.6). Produces 5' phosphate and 3' hydroxyl termini, suggesting it could directly participate in the processing of primary piRNA transcripts. Ref.4 Ref.5 Ref.6 Ref.7

Enzyme regulation

SsDNA hydrolase activity does not depend upon, but it stimulated by, the presence of Ca2+ and Mn2+. Ref.7

Subunit structure

Homodimer. Ref.7

Subcellular location

Mitochondrion outer membrane; Single-pass membrane protein Ref.4.

Tissue specificity

Predominantly expressed in testis (at protein level). Also expressed at high levels in growing ovary. Ref.4

Developmental stage

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). Ref.4 Ref.5

Domain

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.

Disruption phenotype

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. Ref.4 Ref.5

Sequence similarities

Belongs to the phospholipase D family. MitoPLD/Zucchini subfamily.

Contains 1 C3H1-type zinc finger.

Contains 1 PLD phosphodiesterase domain.

Ontologies

Keywords
   Biological processDifferentiation
Lipid degradation
Lipid metabolism
Meiosis
Spermatogenesis
   Cellular componentMembrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionEndonuclease
Hydrolase
Nuclease
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA methylation involved in gamete generation

Inferred from mutant phenotype Ref.4. Source: UniProtKB

P granule organization

Inferred from mutant phenotype Ref.5. Source: UniProtKB

lipid catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

meiotic nuclear division

Inferred from mutant phenotype Ref.4Ref.5. Source: UniProtKB

mitochondrial fusion

Inferred from sequence or structural similarity. Source: UniProtKB

piRNA metabolic process

Inferred from mutant phenotype Ref.4Ref.5. Source: UniProtKB

spermatid development

Inferred from mutant phenotype Ref.4Ref.5. Source: UniProtKB

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial outer membrane

Inferred from direct assay Ref.4. Source: UniProtKB

   Molecular_functioncardiolipin hydrolase activity

Inferred from sequence or structural similarity. Source: UniProtKB

endonuclease activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5SWZ9-1)

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.
Isoform 2 (identifier: Q5SWZ9-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 221221Mitochondrial cardiolipin hydrolase
PRO_0000325911

Regions

Topological domain1 – 44Mitochondrial intermembrane Potential
Transmembrane5 – 2723Helical; Potential
Topological domain28 – 221194Cytoplasmic Potential
Domain148 – 17528PLD phosphodiesterase
Zinc finger44 – 7532C3H1-type; atypical
Region1 – 3838Required for mitochondrial localization

Sites

Active site1531 Potential
Active site1551 Potential
Active site1601 Potential

Natural variations

Alternative sequence139 – 1479AGIQVRHDQ → GYRYGTTRT in isoform 2.
VSP_032474
Alternative sequence148 – 22174Missing in isoform 2.
VSP_032475

Experimental info

Mutagenesis1531H → N: Loss of nuclease activity. Ref.7

Secondary structure

............................... 221
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: A7A2E813281B924E

FASTA22125,041
        10         20         30         40         50         60 
MGRSSWRLVF AAGAGLALAL EALPWLMRWL LAGRRPRREV LFFPSQVTCT EALLQAPGLP 

        70         80         90        100        110        120 
PGPSGCPCSL PHSESSLSRL LRALLAARSS LELCLFAFSS PQLGRAVQLL HQRGVRVRVI 

       130        140        150        160        170        180 
TDCDYMALNG SQIGLLRKAG IQVRHDQDLG YMHHKFAIVD KKVLITGSLN WTTQAIQNNR 

       190        200        210        220 
ENVLIMEDTE YVRLFLEEFE RIWEEFDPTK YSFFPQKHRG H 

« Hide

Isoform 2 [UniParc].

Checksum: C89BFBDAE7BA570D
Show »

FASTA14716,108

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"Structure and function of Zucchini endoribonuclease in piRNA biogenesis."
Nishimasu H., Ishizu H., Saito K., Fukuhara S., Kamatani M.K., Bonnefond L., Matsumoto N., Nishizawa T., Nakanaga K., Aoki J., Ishitani R., Siomi H., Siomi M.C., Nureki O.
Nature 491:284-287(2012) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_898962.2. NM_183139.2.
XP_006532662.1. XM_006532599.1.
UniGeneMm.344651.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4GGJX-ray1.75A31-221[»]
4GGKX-ray2.10A31-221[»]
ProteinModelPortalQ5SWZ9.
SMRQ5SWZ9. Positions 35-209.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59982N.
STRING10090.ENSMUSP00000115503.

PTM databases

PhosphoSiteQ5SWZ9.

Proteomic databases

PaxDbQ5SWZ9.
PRIDEQ5SWZ9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000125307; ENSMUSP00000115503; ENSMUSG00000043648. [Q5SWZ9-1]
GeneID194908.
KEGGmmu:194908.
UCSCuc007jev.1. mouse. [Q5SWZ9-2]
uc011xvp.1. mouse. [Q5SWZ9-1]

Organism-specific databases

CTD201164.
MGIMGI:2687283. Pld6.

Phylogenomic databases

eggNOGCOG1502.
GeneTreeENSGT00390000004368.
HOGENOMHOG000082679.
HOVERGENHBG108267.
InParanoidQ5SWZ9.
KOK16862.
OMAFPSQVTC.
OrthoDBEOG7CNZHW.
PhylomeDBQ5SWZ9.
TreeFamTF332817.

Enzyme and pathway databases

ReactomeREACT_188937. Metabolism.

Gene expression databases

BgeeQ5SWZ9.
GenevestigatorQ5SWZ9.

Family and domain databases

InterProIPR025202. PLD-like_dom.
IPR001736. PLipase_D/transphosphatidylase.
[Graphical view]
PfamPF13091. PLDc_2. 1 hit.
[Graphical view]
SMARTSM00155. PLDc. 1 hit.
[Graphical view]
PROSITEPS50035. PLD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio371672.
PROQ5SWZ9.
SOURCESearch...

Entry information

Entry namePLD6_MOUSE
AccessionPrimary (citable) accession number: Q5SWZ9
Secondary accession number(s): B7ZN71, Q3UTA3, Q8BVM0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: December 21, 2004
Last modified: April 16, 2014
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot