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Protein

Mitochondrial cardiolipin hydrolase

Gene

Pld6

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

Functioni

Endonuclease that plays a critical role in PIWI-interacting RNA (piRNA) biogenesis during spermatogenesis. 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 (PubMed:23064227, PubMed:23064230). Has been proposed to act as a cardiolipin hydrolase to generate phosphatidic acid at mitochondrial surface (PubMed:21397847, 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, 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, PubMed:23064230). Produces 5' phosphate and 3' hydroxyl termini, suggesting it could directly participate in the processing of primary piRNA transcripts (PubMed:23064230). Also acts as a regulator of mitochondrial shape through facilitating mitochondrial fusion (By similarity).By similarity4 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)DescriptionActionsGraphical viewLength
Active sitei153PROSITE-ProRule annotation1
Active sitei155PROSITE-ProRule annotation1
Active sitei160PROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri44 – 75C3H1-type; atypicalAdd BLAST32

GO - Molecular functioni

GO - Biological processi

  • cardiolipin biosynthetic process Source: GO_Central
  • DNA methylation involved in gamete generation Source: UniProtKB
  • lipid catabolic process Source: UniProtKB-KW
  • meiotic nuclear division Source: UniProtKB
  • mitochondrial fusion Source: UniProtKB
  • P granule organization Source: UniProtKB
  • phosphatidylglycerol biosynthetic process Source: Reactome
  • piRNA metabolic process Source: UniProtKB
  • positive regulation of mitochondrial fusion Source: MGI
  • 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

ReactomeiR-MMU-1483148. Synthesis of PG.
R-MMU-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitochondrial cardiolipin hydrolase (EC:3.1.-.-2 Publications)
Alternative name(s):
Choline phosphatase 6
Mitochondrial phospholipaseBy similarity
Short name:
MitoPLDBy similarity
Phosphatidylcholine-hydrolyzing phospholipase D6
Phospholipase D6
Short name:
PLD 6
Protein zucchini homologBy similarity
Short name:
mZuc
Gene namesi
Name:Pld6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2687283. Pld6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 4Mitochondrial intermembraneSequence analysis4
Transmembranei5 – 27HelicalSequence analysisAdd BLAST23
Topological domaini28 – 221CytoplasmicSequence analysisAdd BLAST194

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Mutagenesisi153H → N: Loss of nuclease activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003259111 – 221Mitochondrial cardiolipin hydrolaseAdd BLAST221

Proteomic databases

PaxDbiQ5SWZ9.
PRIDEiQ5SWZ9.

PTM databases

PhosphoSitePlusiQ5SWZ9.

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

BgeeiENSMUSG00000043648.

Interactioni

Subunit structurei

Homodimer (PubMed:23064227). Interacts with MOV10L1 (PubMed:25762440). Interacts with MIGA1 and MIGA2; possibly facilitating homodimer formation (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-59982N.
STRINGi10090.ENSMUSP00000115503.

Structurei

Secondary structure

1221
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 44Combined sources7
Turni51 – 55Combined sources5
Beta strandi68 – 70Combined sources3
Helixi76 – 85Combined sources10
Beta strandi88 – 96Combined sources9
Helixi101 – 112Combined sources12
Beta strandi116 – 123Combined sources8
Helixi132 – 138Combined sources7
Beta strandi142 – 145Combined sources4
Beta strandi148 – 150Combined sources3
Beta strandi155 – 159Combined sources5
Turni160 – 162Combined sources3
Beta strandi163 – 168Combined sources6
Helixi173 – 178Combined sources6
Beta strandi181 – 186Combined sources6
Helixi189 – 205Combined sources17

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini148 – 175PLD phosphodiesterasePROSITE-ProRule annotationAdd BLAST28

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 38Required for mitochondrial localizationAdd BLAST38

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)DescriptionActionsGraphical viewLength
Zinc fingeri44 – 75C3H1-type; atypicalAdd BLAST32

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiENOG410J0H4. Eukaryota.
COG1502. LUCA.
GeneTreeiENSGT00390000004368.
HOGENOMiHOG000082679.
HOVERGENiHBG108267.
InParanoidiQ5SWZ9.
KOiK16862.
OMAiPRREVLF.
OrthoDBiEOG091G0FI5.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_032474139 – 147AGIQVRHDQ → GYRYGTTRT in isoform 2. 2 Publications9
Alternative sequenceiVSP_032475148 – 221Missing in isoform 2. 2 PublicationsAdd BLAST74

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.
CCDSiCCDS70199.1. [Q5SWZ9-1]
RefSeqiNP_001277212.1. NM_001290283.1. [Q5SWZ9-1]
NP_898962.2. NM_183139.2. [Q5SWZ9-2]
UniGeneiMm.344651.

3D structure databases

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

Protein-protein interaction databases

DIPiDIP-59982N.
STRINGi10090.ENSMUSP00000115503.

PTM databases

PhosphoSitePlusiQ5SWZ9.

Proteomic databases

PaxDbiQ5SWZ9.
PRIDEiQ5SWZ9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi201164.
MGIiMGI:2687283. Pld6.

Phylogenomic databases

eggNOGiENOG410J0H4. Eukaryota.
COG1502. LUCA.
GeneTreeiENSGT00390000004368.
HOGENOMiHOG000082679.
HOVERGENiHBG108267.
InParanoidiQ5SWZ9.
KOiK16862.
OMAiPRREVLF.
OrthoDBiEOG091G0FI5.
PhylomeDBiQ5SWZ9.
TreeFamiTF332817.

Enzyme and pathway databases

ReactomeiR-MMU-1483148. Synthesis of PG.
R-MMU-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Miscellaneous databases

PROiQ5SWZ9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000043648.

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]
ProtoNetiSearch...

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 2, 2016
This is version 99 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.