UniProtKB - Q8N2A8 (PLD6_HUMAN)
Protein
Mitochondrial cardiolipin hydrolase
Gene
PLD6
Organism
Homo sapiens (Human)
Status
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 (By similarity). 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 (By similarity). Has been proposed to act as a cardiolipin hydrolase to generate phosphatidic acid at mitochondrial surface (By similarity). 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 (PubMed:21397848). In addition, cardiolipin is almost exclusively found on the inner mitochondrial membrane, while PLD6 localizes to the outer mitochondrial membrane, facing the cytosol (PubMed:21397848). Has been shown to be a backbone-non-specific, single strand-specific nuclease, cleaving either RNA or DNA substrates with similar affinity. Produces 5' phosphate and 3' hydroxyl termini, suggesting it could directly participate in the processing of primary piRNA transcripts (By similarity). Also acts as a regulator of mitochondrial shape through facilitating mitochondrial fusion (PubMed:17028579, PubMed:26711011).By similarity3 Publications
Activity regulationi
SsDNA hydrolase activity does not depend upon, but it stimulated by, the presence of Ca2+ and Mn2+.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 156 | Curated | 1 | |
Active sitei | 158 | PROSITE-ProRule annotation | 1 | |
Active sitei | 163 | PROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 45 – 78 | C3H1-type; atypicalAdd BLAST | 34 |
GO - Molecular functioni
- cardiolipin hydrolase activity Source: UniProtKB
- endonuclease activity Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- protein homodimerization activity Source: UniProtKB
GO - Biological processi
- DNA methylation involved in gamete generation Source: UniProtKB
- lipid catabolic process Source: UniProtKB-KW
- meiotic cell cycle Source: UniProtKB
- mitochondrial fusion Source: UniProtKB
- P granule organization Source: UniProtKB
- phosphatidic acid biosynthetic process Source: Reactome
- piRNA metabolic process Source: UniProtKB
- positive regulation of mitochondrial fusion Source: MGI
- spermatid development Source: UniProtKB
Keywordsi
Molecular function | Endonuclease, Hydrolase, Nuclease |
Biological process | Differentiation, Lipid degradation, Lipid metabolism, Meiosis, Spermatogenesis |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q8N2A8 |
Reactomei | R-HSA-1483148, Synthesis of PG R-HSA-1483166, Synthesis of PA R-HSA-5601884, PIWI-interacting RNA (piRNA) biogenesis |
Names & Taxonomyi
Protein namesi | Recommended name: Mitochondrial cardiolipin hydrolase (EC:3.1.-.-By similarity)Alternative name(s): Choline phosphatase 6 Mitochondrial phospholipase1 Publication Short name: MitoPLD1 Publication Phosphatidylcholine-hydrolyzing phospholipase D6 Phospholipase D6 Short name: PLD 6 Protein zucchini homologBy similarity |
Gene namesi | Name:PLD6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000179598.5 |
HGNCi | HGNC:30447, PLD6 |
MIMi | 614960, gene |
neXtProti | NX_Q8N2A8 |
Subcellular locationi
Mitochondrion
- Mitochondrion outer membrane 1 Publication; Single-pass membrane protein 1 Publication
Mitochondrion
- mitochondrial outer membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 4 | Mitochondrial intermembraneSequence analysis | 4 | |
Transmembranei | 5 – 27 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 28 – 252 | CytoplasmicSequence analysisAdd BLAST | 225 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion outer membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 156 | H → N: Mitochondrial fragmentation. No apoptosis, no alterations of cell homeostasis. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 201164 |
OpenTargetsi | ENSG00000179598 |
PharmGKBi | PA164724625 |
Miscellaneous databases
Pharosi | Q8N2A8, Tbio |
Polymorphism and mutation databases
BioMutai | PLD6 |
DMDMi | 74728697 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000325910 | 1 – 252 | Mitochondrial cardiolipin hydrolaseAdd BLAST | 252 |
Proteomic databases
EPDi | Q8N2A8 |
MassIVEi | Q8N2A8 |
MaxQBi | Q8N2A8 |
PaxDbi | Q8N2A8 |
PeptideAtlasi | Q8N2A8 |
PRIDEi | Q8N2A8 |
ProteomicsDBi | 71671 |
PTM databases
iPTMneti | Q8N2A8 |
PhosphoSitePlusi | Q8N2A8 |
SwissPalmi | Q8N2A8 |
Expressioni
Tissue specificityi
Widely expressed. Expression is not limited to testis and ovary.2 Publications
Gene expression databases
Bgeei | ENSG00000179598, Expressed in female gonad and 187 other tissues |
Genevisiblei | Q8N2A8, HS |
Organism-specific databases
HPAi | ENSG00000179598, Tissue enhanced (testis) |
Interactioni
Subunit structurei
GO - Molecular functioni
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 128367, 22 interactors |
IntActi | Q8N2A8, 12 interactors |
STRINGi | 9606.ENSP00000317177 |
Miscellaneous databases
RNActi | Q8N2A8, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 151 – 178 | PLD phosphodiesterasePROSITE-ProRule annotationAdd BLAST | 28 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 39 | Required for mitochondrial localizationAdd BLAST | 39 |
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.1 Publication
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 45 – 78 | C3H1-type; atypicalAdd BLAST | 34 |
Keywords - Domaini
Transmembrane, Transmembrane helix, Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502RXG9, Eukaryota |
GeneTreei | ENSGT00390000004368 |
HOGENOMi | CLU_080814_0_1_1 |
InParanoidi | Q8N2A8 |
OMAi | CSLPHGE |
OrthoDBi | 1489926at2759 |
PhylomeDBi | Q8N2A8 |
TreeFami | TF332817 |
Family and domain databases
InterProi | View protein in InterPro IPR025202, PLD-like_dom IPR001736, PLipase_D/transphosphatidylase |
Pfami | View protein in Pfam PF13091, PLDc_2, 1 hit |
SMARTi | View protein in SMART SM00155, PLDc, 1 hit |
PROSITEi | View protein in PROSITE PS50035, PLD, 1 hit |
i Sequence
Sequence statusi: Complete.
Q8N2A8-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGRLSWQVAA AAAVGLALTL EALPWVLRWL RSRRRRPRRE ALFFPSQVTC
60 70 80 90 100
TEALLRAPGA ELAELPEGCP CGLPHGESAL SRLLRALLAA RASLDLCLFA
110 120 130 140 150
FSSPQLGRAV QLLHQRGVRV RVVTDCDYMA LNGSQIGLLR KAGIQVRHDQ
160 170 180 190 200
DPGYMHHKFA IVDKRVLITG SLNWTTQAIQ NNRENVLITE DDEYVRLFLE
210 220 230 240 250
EFERIWEQFN PTKYTFFPPK KSHGSCAPPV SRAGGRLLSW HRTCGTSSES
QT
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_039951 | 42 | L → P1 PublicationCorresponds to variant dbSNP:rs17856924Ensembl. | 1 | |
Natural variantiVAR_039952 | 108 | R → H1 PublicationCorresponds to variant dbSNP:rs11551966Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK090899 mRNA Translation: BAC03541.1 AC055811 Genomic DNA No translation available. BC031263 mRNA Translation: AAH31263.1 |
CCDSi | CCDS11182.1 |
RefSeqi | NP_849158.2, NM_178836.3 |
Genome annotation databases
Ensembli | ENST00000321560; ENSP00000317177; ENSG00000179598 |
GeneIDi | 201164 |
KEGGi | hsa:201164 |
UCSCi | uc002gqz.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK090899 mRNA Translation: BAC03541.1 AC055811 Genomic DNA No translation available. BC031263 mRNA Translation: AAH31263.1 |
CCDSi | CCDS11182.1 |
RefSeqi | NP_849158.2, NM_178836.3 |
3D structure databases
SMRi | Q8N2A8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 128367, 22 interactors |
IntActi | Q8N2A8, 12 interactors |
STRINGi | 9606.ENSP00000317177 |
PTM databases
iPTMneti | Q8N2A8 |
PhosphoSitePlusi | Q8N2A8 |
SwissPalmi | Q8N2A8 |
Polymorphism and mutation databases
BioMutai | PLD6 |
DMDMi | 74728697 |
Proteomic databases
EPDi | Q8N2A8 |
MassIVEi | Q8N2A8 |
MaxQBi | Q8N2A8 |
PaxDbi | Q8N2A8 |
PeptideAtlasi | Q8N2A8 |
PRIDEi | Q8N2A8 |
ProteomicsDBi | 71671 |
Protocols and materials databases
Antibodypediai | 63312, 84 antibodies |
Genome annotation databases
Ensembli | ENST00000321560; ENSP00000317177; ENSG00000179598 |
GeneIDi | 201164 |
KEGGi | hsa:201164 |
UCSCi | uc002gqz.4, human |
Organism-specific databases
CTDi | 201164 |
DisGeNETi | 201164 |
EuPathDBi | HostDB:ENSG00000179598.5 |
GeneCardsi | PLD6 |
HGNCi | HGNC:30447, PLD6 |
HPAi | ENSG00000179598, Tissue enhanced (testis) |
MIMi | 614960, gene |
neXtProti | NX_Q8N2A8 |
OpenTargetsi | ENSG00000179598 |
PharmGKBi | PA164724625 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RXG9, Eukaryota |
GeneTreei | ENSGT00390000004368 |
HOGENOMi | CLU_080814_0_1_1 |
InParanoidi | Q8N2A8 |
OMAi | CSLPHGE |
OrthoDBi | 1489926at2759 |
PhylomeDBi | Q8N2A8 |
TreeFami | TF332817 |
Enzyme and pathway databases
PathwayCommonsi | Q8N2A8 |
Reactomei | R-HSA-1483148, Synthesis of PG R-HSA-1483166, Synthesis of PA R-HSA-5601884, PIWI-interacting RNA (piRNA) biogenesis |
Miscellaneous databases
BioGRID-ORCSi | 201164, 3 hits in 849 CRISPR screens |
ChiTaRSi | PLD6, human |
GenomeRNAii | 201164 |
Pharosi | Q8N2A8, Tbio |
PROi | PR:Q8N2A8 |
RNActi | Q8N2A8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000179598, Expressed in female gonad and 187 other tissues |
Genevisiblei | Q8N2A8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR025202, PLD-like_dom IPR001736, PLipase_D/transphosphatidylase |
Pfami | View protein in Pfam PF13091, PLDc_2, 1 hit |
SMARTi | View protein in SMART SM00155, PLDc, 1 hit |
PROSITEi | View protein in PROSITE PS50035, PLD, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PLD6_HUMAN | |
Accessioni | Q8N2A8Primary (citable) accession number: Q8N2A8 Secondary accession number(s): Q8N5Y1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 18, 2008 |
Last sequence update: | October 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations