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Protein

Mitochondrial cardiolipin hydrolase

Gene

PLD6

Organism
Homo sapiens (Human)
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 (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

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei156 – 1561Curated
Active sitei158 – 1581PROSITE-ProRule annotation
Active sitei163 – 1631PROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri45 – 7834C3H1-type; atypicalAdd
BLAST

GO - Molecular functioni

  • cardiolipin hydrolase activity Source: UniProtKB
  • cardiolipin synthase activity Source: GO_Central
  • endoribonuclease activity Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

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-HSA-1483148. Synthesis of PG.
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:30447. PLD6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 44Mitochondrial intermembraneSequence analysis
Transmembranei5 – 2723HelicalSequence analysisAdd
BLAST
Topological domaini28 – 252225CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • mitochondrial outer membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi156 – 1561H → N: Mitochondrial fragmentation. No apoptosis, no alterations of cell homeostasis. 2 Publications

Organism-specific databases

PharmGKBiPA164724625.

Polymorphism and mutation databases

BioMutaiPLD6.
DMDMi74728697.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 252252Mitochondrial cardiolipin hydrolasePRO_0000325910Add
BLAST

Proteomic databases

EPDiQ8N2A8.
MaxQBiQ8N2A8.
PaxDbiQ8N2A8.
PRIDEiQ8N2A8.

PTM databases

iPTMnetiQ8N2A8.
PhosphoSiteiQ8N2A8.
SwissPalmiQ8N2A8.

Expressioni

Tissue specificityi

Widely expressed. Expression is not limited to testis and ovary.2 Publications

Gene expression databases

BgeeiQ8N2A8.
CleanExiHS_PLD6.
GenevisibleiQ8N2A8. HS.

Organism-specific databases

HPAiHPA049345.

Interactioni

Subunit structurei

Homodimer (PubMed:17028579). Interacts with MOV10L1 (By similarity). Interacts with FAM73A/MIGA1 and FAM73B/MIGA2; possibly facilitating homodimer formation (PubMed:26711011).By similarity2 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi128367. 12 interactions.
STRINGi9606.ENSP00000317177.

Structurei

3D structure databases

ProteinModelPortaliQ8N2A8.
SMRiQ8N2A8. Positions 36-212.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini151 – 17828PLD phosphodiesterasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 3939Required 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.1 Publication

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 fingeri45 – 7834C3H1-type; atypicalAdd
BLAST

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiENOG410J0H4. Eukaryota.
COG1502. LUCA.
GeneTreeiENSGT00390000004368.
HOGENOMiHOG000082679.
HOVERGENiHBG108267.
InParanoidiQ8N2A8.
KOiK16862.
OMAiPRREVLF.
OrthoDBiEOG7CNZHW.
PhylomeDBiQ8N2A8.
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]

Sequencei

Sequence statusi: Complete.

Q8N2A8-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:252
Mass (Da):28,273
Last modified:October 1, 2002 - v1
Checksum:iCE3A205C1D42B497
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti42 – 421L → P.1 Publication
Corresponds to variant rs17856924 [ dbSNP | Ensembl ].
VAR_039951
Natural varianti108 – 1081R → H.1 Publication
Corresponds to variant rs11551966 [ dbSNP | Ensembl ].
VAR_039952

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.
CCDSiCCDS11182.1.
RefSeqiNP_849158.2. NM_178836.3.
UniGeneiHs.729079.

Genome annotation databases

EnsembliENST00000321560; ENSP00000317177; ENSG00000179598.
GeneIDi201164.
KEGGihsa:201164.
UCSCiuc002gqz.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS11182.1.
RefSeqiNP_849158.2. NM_178836.3.
UniGeneiHs.729079.

3D structure databases

ProteinModelPortaliQ8N2A8.
SMRiQ8N2A8. Positions 36-212.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128367. 12 interactions.
STRINGi9606.ENSP00000317177.

PTM databases

iPTMnetiQ8N2A8.
PhosphoSiteiQ8N2A8.
SwissPalmiQ8N2A8.

Polymorphism and mutation databases

BioMutaiPLD6.
DMDMi74728697.

Proteomic databases

EPDiQ8N2A8.
MaxQBiQ8N2A8.
PaxDbiQ8N2A8.
PRIDEiQ8N2A8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321560; ENSP00000317177; ENSG00000179598.
GeneIDi201164.
KEGGihsa:201164.
UCSCiuc002gqz.4. human.

Organism-specific databases

CTDi201164.
GeneCardsiPLD6.
HGNCiHGNC:30447. PLD6.
HPAiHPA049345.
MIMi614960. gene.
neXtProtiNX_Q8N2A8.
PharmGKBiPA164724625.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0H4. Eukaryota.
COG1502. LUCA.
GeneTreeiENSGT00390000004368.
HOGENOMiHOG000082679.
HOVERGENiHBG108267.
InParanoidiQ8N2A8.
KOiK16862.
OMAiPRREVLF.
OrthoDBiEOG7CNZHW.
PhylomeDBiQ8N2A8.
TreeFamiTF332817.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiPLD6. human.
GenomeRNAii201164.
NextBioi90067.
PROiQ8N2A8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N2A8.
CleanExiHS_PLD6.
GenevisibleiQ8N2A8. HS.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Amygdala.
  2. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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], VARIANTS PRO-42 AND HIS-108.
    Tissue: Brain.
  4. "A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis."
    Choi S.Y., Huang P., Jenkins G.M., Chan D.C., Schiller J., Frohman M.A.
    Nat. Cell Biol. 8:1255-1262(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, HOMODIMERIZATION, TISSUE SPECIFICITY, MUTAGENESIS OF HIS-156.
  5. "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: TISSUE SPECIFICITY.
  6. "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, MUTAGENESIS OF HIS-156.
  7. "Mitoguardin regulates mitochondrial fusion through MitoPLD and is required for neuronal homeostasis."
    Zhang Y., Liu X., Bai J., Tian X., Zhao X., Liu W., Duan X., Shang W., Fan H.Y., Tong C.
    Mol. Cell 61:111-124(2016) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FAM73A AND FAM73B.

Entry informationi

Entry nameiPLD6_HUMAN
AccessioniPrimary (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: March 16, 2016
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.