Q5SWZ9 (PLD6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial cardiolipin hydrolase
EC=3.1.4.-

Alternative name(s):
Choline phosphatase 6
Mitochondrial phospholipase
Short name=MitoPLD
Phosphatidylcholine-hydrolyzing phospholipase D6
Phospholipase D6
Short name=PLD 6

Gene names

Name:

Pld6

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	221 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Cardiolipin hydrolase present at the mitochondrial outer membrane required both for mitochondrial fusion and piRNA metabolic process. Acts by catalyzing the hydrolysis of cardiolipin (diphosphatidylglycerol) to form phosphatidate (phosphatidic acid or PA) at the mitochondrial outer membrane surface, promoting mitochondrial fusion. The production of phosphatidate also regulates the piRNA metabolic process by promoting recruitment and/or activation of components of the meiotic nuage, also named P granule, a critical step for primary biogenesis of piRNAs. Required during spermatogenesis to repress transposable elements and prevent their mobilization via its role in the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Ref.4 Ref.5
Subunit structure	Homodimer By similarity.
Subcellular location	Mitochondrion outer membrane; Single-pass membrane protein Ref.4.
Tissue specificity	Mainly expressed in testis and ovary. Ref.4
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	Male sterility 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 PLD phosphodiesterase domain.

Ontologies

Keywords
Biological process	Differentiation Lipid degradation Meiosis Spermatogenesis
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA 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 meiosis 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 component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from direct assay Ref.4. Source: UniProtKB
Molecular function	cardiolipin hydrolase activity Inferred from sequence or structural similarity. Source: UniProtKB 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 221	221	Mitochondrial cardiolipin hydrolase		PRO_0000325911
Regions
	Topological domain	1 – 4	4	Mitochondrial intermembrane Potential
	Transmembrane	5 – 27	23	Helical; Potential
	Topological domain	28 – 221	194	Cytoplasmic Potential
	Domain	148 – 175	28	PLD phosphodiesterase
Sites
	Active site	153	1	Potential
	Active site	155	1	Potential
	Active site	160	1	Potential
Natural variations
	Alternative sequence	139 – 147	9	AGIQVRHDQ → GYRYGTTRT in isoform 2.		VSP_032474
	Alternative sequence	148 – 221	74	Missing in isoform 2.		VSP_032475

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: A7A2E813281B924E	FASTA	221	25,041
	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
	Isoform 2 [UniParc]. Checksum: C89BFBDAE7BA570D	FASTA	147	16,108
	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 TDCDYMALNG SQIGLLRKGY RYGTTRT

References

	« Hide 'large scale' referencesShow '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. , 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: 16141072] [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. , 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: 19468303] [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: 15489334] [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: 21397847] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[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: 21397848] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	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.
IPI	IPI00225919. IPI00889236.
RefSeq	NP_898962.2. NM_183139.2.
UniGene	Mm.344651.
3D structure databases
ProteinModelPortal	Q5SWZ9.
SMR	Q5SWZ9. Positions 74-210.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5SWZ9.
Proteomic databases
PRIDE	Q5SWZ9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000125307; ENSMUSP00000115503; ENSMUSG00000043648.
GeneID	194908.
KEGG	mmu:194908.
UCSC	uc007jev.1. mouse. uc011xvp.1. mouse.
Organism-specific databases
CTD	201164.
MGI	MGI:2687283. Pld6.
Phylogenomic databases
eggNOG	roNOG08350.
GeneTree	ENSGT00390000004368.
HOGENOM	HBG714389.
HOVERGEN	HBG108267.
InParanoid	Q5SWZ9.
OMA	PRREVLF.
OrthoDB	EOG402WTD.
Gene expression databases
ArrayExpress	Q5SWZ9.
Bgee	Q5SWZ9.
Genevestigator	Q5SWZ9.
Family and domain databases
InterPro	IPR001736. PLipase_D/transphosphatidylase. [Graphical view]
SMART	SM00155. PLDc. 1 hit. [Graphical view]
PROSITE	PS50035. PLD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	371672.
SOURCE	Search...

Entry information

Entry name

PLD6_MOUSE

Accession

Primary (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:	September 21, 2011
This is version 57 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program