Q8N2A8 (PLD6_HUMAN) 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
Protein zucchini homolog

Gene names

Name:

PLD6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	252 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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.6
Subunit structure	Homodimer. Ref.4
Subcellular location	Mitochondrion outer membrane; Single-pass membrane protein Ref.4.
Tissue specificity	Widely expressed. Expression is not limites to testis and ovary. 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 (Ref.4).
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	Polymorphism
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 sequence or structural similarity. Source: UniProtKB P granule organization Inferred from sequence or structural similarity. Source: UniProtKB lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW meiosis Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial fusion Inferred from mutant phenotype Ref.4. Source: UniProtKB piRNA metabolic process Inferred from sequence or structural similarity. Source: UniProtKB spermatid development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from direct assay Ref.4Ref.6. Source: UniProtKB
Molecular function	cardiolipin hydrolase activity Inferred from direct assay Ref.4Ref.6. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 252	252	Mitochondrial cardiolipin hydrolase		PRO_0000325910
Regions
	Topological domain	1 – 4	4	Mitochondrial intermembrane Potential
	Transmembrane	5 – 27	23	Helical; Potential
	Topological domain	28 – 252	225	Cytoplasmic Potential
	Domain	151 – 178	28	PLD phosphodiesterase
Sites
	Active site	156	1	Probable
	Active site	158	1	Potential
	Active site	163	1	Potential
Natural variations
	Natural variant	42	1	L → P. Ref.3 Corresponds to variant rs17856924 [ dbSNP | Ensembl ].		VAR_039951
	Natural variant	108	1	R → H. Ref.3 Corresponds to variant rs11551966 [ dbSNP | Ensembl ].		VAR_039952
Experimental info
	Mutagenesis	156	1	H → N: Abolishes cardiolipin hydrolase activity. Ref.4 Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q8N2A8 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: CE3A205C1D42B497	FASTA	252	28,273
	10 20 30 40 50 60 MGRLSWQVAA AAAVGLALTL EALPWVLRWL RSRRRRPRRE ALFFPSQVTC TEALLRAPGA 70 80 90 100 110 120 ELAELPEGCP CGLPHGESAL SRLLRALLAA RASLDLCLFA FSSPQLGRAV QLLHQRGVRV 130 140 150 160 170 180 RVVTDCDYMA LNGSQIGLLR KAGIQVRHDQ DPGYMHHKFA IVDKRVLITG SLNWTTQAIQ 190 200 210 220 230 240 NNRENVLITE DDEYVRLFLE EFERIWEQFN PTKYTFFPPK KSHGSCAPPV SRAGGRLLSW 250 HRTCGTSSES QT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 14702039] [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: 16625196] [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: 15489334] [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: 17028579] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, 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: 21397847] [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: 21397848] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF HIS-156.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK090899 mRNA. Translation: BAC03541.1. AC055811 Genomic DNA. No translation available. BC031263 mRNA. Translation: AAH31263.1.
IPI	IPI00251454.
RefSeq	NP_849158.2. NM_178836.3.
UniGene	Hs.729079.
3D structure databases
ProteinModelPortal	Q8N2A8.
SMR	Q8N2A8. Positions 77-213.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8N2A8.
Polymorphism databases
DMDM	74728697.
Proteomic databases
PRIDE	Q8N2A8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000321560; ENSP00000317177; ENSG00000179598.
GeneID	201164.
KEGG	hsa:201164.
UCSC	uc002gqz.1. human.
Organism-specific databases
CTD	201164.
GeneCards	GC17M017048.
HGNC	HGNC:30447. PLD6.
neXtProt	NX_Q8N2A8.
PharmGKB	PA164724625.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11656.
GeneTree	ENSGT00390000004368.
HOGENOM	HBG714389.
HOVERGEN	HBG108267.
InParanoid	Q8N2A8.
OMA	PRREVLF.
OrthoDB	EOG402WTD.
PhylomeDB	Q8N2A8.
Gene expression databases
ArrayExpress	Q8N2A8.
Bgee	Q8N2A8.
CleanEx	HS_PLD6.
Genevestigator	Q8N2A8.
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	90067.

Entry information

Entry name

PLD6_HUMAN

Accession

Primary (citable) accession number: Q8N2A8
Secondary accession number(s): Q8N5Y1

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	October 1, 2002
Last modified:	January 25, 2012
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.