O14939 (PLD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phospholipase D2
Short name=PLD 2
Short name=hPLD2
EC=3.1.4.4

Alternative name(s):
Choline phosphatase 2
PLD1C
Phosphatidylcholine-hydrolyzing phospholipase D2

Gene names

Name:

PLD2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	933 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May have a role in signal-induced cytoskeletal regulation and/or endocytosis By similarity.
Catalytic activity	A phosphatidylcholine + H2O = choline + a phosphatidate.
Enzyme regulation	Stimulated by phosphatidylinositol 4,5-bisphosphate and activated by the ADP-ribosylation factor-1 (ARF-1).
Subunit structure	Interacts with EGFR By similarity. Interacts with PIP5K1B. Ref.5
Subcellular location	Membrane; Peripheral membrane protein By similarity.
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylated by FGR By similarity.
Sequence similarities	Belongs to the phospholipase D family. Contains 1 PH domain. Contains 2 PLD phosphodiesterase domains. Contains 1 PX (phox homology) domain.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Fc-gamma receptor signaling pathway involved in phagocytosis Traceable author statement. Source: Reactome G-protein coupled receptor internalization Inferred from electronic annotation. Source: Compara cytoskeleton organization Traceable author statement PubMed 9395408. Source: ProtInc innate immune response Traceable author statement. Source: Reactome lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phosphatidic acid biosynthetic process Traceable author statement. Source: Reactome phosphatidylglycerol biosynthetic process Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement Ref.2. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	brush border membrane Inferred from electronic annotation. Source: Compara endoplasmic reticulum membrane Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	NAPE-specific phospholipase D activity Inferred from electronic annotation. Source: EC phosphatidylinositol binding Inferred from electronic annotation. Source: InterPro phospholipase D activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	4	EBI-1053996,EBI-401755

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform PLD2A (identifier: O14939-1)

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 PLD2B (identifier: O14939-2)

The sequence of this isoform differs from the canonical sequence as follows:
     810-820: Missing.

Isoform PLD2C (identifier: O14939-3)

The sequence of this isoform differs from the canonical sequence as follows:
     337-933: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 933	933	Phospholipase D2		PRO_0000218805
Regions
	Domain	65 – 195	131	PX
	Domain	203 – 311	109	PH
	Domain	437 – 464	28	PLD phosphodiesterase 1
	Domain	751 – 778	28	PLD phosphodiesterase 2
	Region	441 – 788	348	Catalytic
Natural variations
	Alternative sequence	337 – 933	597	Missing in isoform PLD2C.		VSP_005027
	Alternative sequence	810 – 820	11	Missing in isoform PLD2B.		VSP_005028
	Natural variant	172	1	R → C. Ref.1 Ref.4 Corresponds to variant rs2286672 [ dbSNP | Ensembl ].		VAR_051704
	Natural variant	577	1	T → I. Ref.2 Ref.4 Corresponds to variant rs1052748 [ dbSNP | Ensembl ].		VAR_051705
	Natural variant	632	1	E → G. Ref.3 Ref.4 Corresponds to variant rs17854914 [ dbSNP | Ensembl ].		VAR_061750
	Natural variant	804	1	A → T. Corresponds to variant rs11545163 [ dbSNP | Ensembl ].		VAR_051706
	Natural variant	807	1	Q → E in a breast cancer sample; somatic mutation. Ref.6		VAR_036503
	Natural variant	821	1	G → R. Corresponds to variant rs3764897 [ dbSNP | Ensembl ].		VAR_051707
	Natural variant	821	1	G → S. Ref.3 Corresponds to variant rs3764897 [ dbSNP | Ensembl ].		VAR_059774
Experimental info
	Sequence conflict	16	1	D → G in AAB96656. Ref.3
	Sequence conflict	165	1	Y → C in AAB96656. Ref.3
	Sequence conflict	212	1	R → C in AAB96656. Ref.3
	Sequence conflict	268	1	Q → R in AAB96655. Ref.3
	Sequence conflict	325	1	S → R in AAB96656. Ref.3
	Sequence conflict	445	1	L → P in AAB96656. Ref.3
	Sequence conflict	510	1	D → G in AAB96656. Ref.3
	Sequence conflict	566	1	T → I in AAB96655. Ref.3
	Sequence conflict	784	1	D → G in AAB96656. Ref.3
	Sequence conflict	801 – 802	2	MN → ID in AAC24498. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform PLD2A [UniParc]. Last modified February 21, 2001. Version 2. Checksum: F25F6B73B45F57ED	FASTA	933	105,987
	10 20 30 40 50 60 MTATPESLFP TGDELDSSQL QMESDEVDTL KEGEDPADRM HPFLAIYELQ SLKVHPLVFA 70 80 90 100 110 120 PGVPVTAQVV GTERYTSGSK VGTCTLYSVR LTHGDFSWTT KKKYRHFQEL HRDLLRHKVL 130 140 150 160 170 180 MSLLPLARFA VAYSPARDAG NREMPSLPRA GPEGSTRHAA SKQKYLENYL NRLLTMSFYR 190 200 210 220 230 240 NYHAMTEFLE VSQLSFIPDL GRKGLEGMIR KRSGGHRVPG LTCCGRDQVC YRWSKRWLVV 250 260 270 280 290 300 KDSFLLYMCL ETGAISFVQL FDPGFEVQVG KRSTEARHGV RIDTSHRSLI LKCSSYRQAR 310 320 330 340 350 360 WWAQEITELA QGPGRDFLQL HRHDSYAPPR PGTLARWFVN GAGYFAAVAD AILRAQEEIF 370 380 390 400 410 420 ITDWWLSPEV YLKRPAHSDD WRLDIMLKRK AEEGVRVSIL LFKEVELALG INSGYSKRAL 430 440 450 460 470 480 MLLHPNIKVM RHPDQVTLWA HHEKLLVVDQ VVAFLGGLDL AYGRWDDLHY RLTDLGDSSE 490 500 510 520 530 540 SAASQPPTPR PDSPATPDLS HNQFFWLGKD YSNLITKDWV QLDRPFEDFI DRETTPRMPW 550 560 570 580 590 600 RDVGVVVHGL PARDLARHFI QRWNFTKTTK AKYKTPTYPY LLPKSTSTAN QLPFTLPGGQ 610 620 630 640 650 660 CTTVQVLRSV DRWSAGTLEN SILNAYLHTI RESQHFLYIE NQFFISCSDG RTVLNKVGDE 670 680 690 700 710 720 IVDRILKAHK QGWCYRVYVL LPLLPGFEGD ISTGGGNSIQ AILHFTYRTL CRGEYSILHR 730 740 750 760 770 780 LKAAMGTAWR DYISICGLRT HGELGGHPVS ELIYIHSKVL IADDRTVIIG SANINDRSLL 790 800 810 820 830 840 GKRDSELAVL IEDTETEPSL MNGAEYQAGR FALSLRKHCF GVILGANTRP DLDLRDPICD 850 860 870 880 890 900 DFFQLWQDMA ESNANIYEQI FRCLPSNATR SLRTLREYVA VEPLATVSPP LARSELTQVQ 910 920 930 GHLVHFPLKF LEDESLLPPL GSKEGMIPLE VWT
	Isoform PLD2B [UniParc]. Checksum: 6E0D388D73E222AF	FASTA	922	104,627
	10 20 30 40 50 60 MTATPESLFP TGDELDSSQL QMESDEVDTL KEGEDPADRM HPFLAIYELQ SLKVHPLVFA 70 80 90 100 110 120 PGVPVTAQVV GTERYTSGSK VGTCTLYSVR LTHGDFSWTT KKKYRHFQEL HRDLLRHKVL 130 140 150 160 170 180 MSLLPLARFA VAYSPARDAG NREMPSLPRA GPEGSTRHAA SKQKYLENYL NRLLTMSFYR 190 200 210 220 230 240 NYHAMTEFLE VSQLSFIPDL GRKGLEGMIR KRSGGHRVPG LTCCGRDQVC YRWSKRWLVV 250 260 270 280 290 300 KDSFLLYMCL ETGAISFVQL FDPGFEVQVG KRSTEARHGV RIDTSHRSLI LKCSSYRQAR 310 320 330 340 350 360 WWAQEITELA QGPGRDFLQL HRHDSYAPPR PGTLARWFVN GAGYFAAVAD AILRAQEEIF 370 380 390 400 410 420 ITDWWLSPEV YLKRPAHSDD WRLDIMLKRK AEEGVRVSIL LFKEVELALG INSGYSKRAL 430 440 450 460 470 480 MLLHPNIKVM RHPDQVTLWA HHEKLLVVDQ VVAFLGGLDL AYGRWDDLHY RLTDLGDSSE 490 500 510 520 530 540 SAASQPPTPR PDSPATPDLS HNQFFWLGKD YSNLITKDWV QLDRPFEDFI DRETTPRMPW 550 560 570 580 590 600 RDVGVVVHGL PARDLARHFI QRWNFTKTTK AKYKTPTYPY LLPKSTSTAN QLPFTLPGGQ 610 620 630 640 650 660 CTTVQVLRSV DRWSAGTLEN SILNAYLHTI RESQHFLYIE NQFFISCSDG RTVLNKVGDE 670 680 690 700 710 720 IVDRILKAHK QGWCYRVYVL LPLLPGFEGD ISTGGGNSIQ AILHFTYRTL CRGEYSILHR 730 740 750 760 770 780 LKAAMGTAWR DYISICGLRT HGELGGHPVS ELIYIHSKVL IADDRTVIIG SANINDRSLL 790 800 810 820 830 840 GKRDSELAVL IEDTETEPSL MNGAEYQAGG VILGANTRPD LDLRDPICDD FFQLWQDMAE 850 860 870 880 890 900 SNANIYEQIF RCLPSNATRS LRTLREYVAV EPLATVSPPL ARSELTQVQG HLVHFPLKFL 910 920 EDESLLPPLG SKEGMIPLEV WT
	Isoform PLD2C [UniParc]. Checksum: B88330C3765169E3	FASTA	336	38,252
	10 20 30 40 50 60 MTATPESLFP TGDELDSSQL QMESDEVDTL KEGEDPADRM HPFLAIYELQ SLKVHPLVFA 70 80 90 100 110 120 PGVPVTAQVV GTERYTSGSK VGTCTLYSVR LTHGDFSWTT KKKYRHFQEL HRDLLRHKVL 130 140 150 160 170 180 MSLLPLARFA VAYSPARDAG NREMPSLPRA GPEGSTRHAA SKQKYLENYL NRLLTMSFYR 190 200 210 220 230 240 NYHAMTEFLE VSQLSFIPDL GRKGLEGMIR KRSGGHRVPG LTCCGRDQVC YRWSKRWLVV 250 260 270 280 290 300 KDSFLLYMCL ETGAISFVQL FDPGFEVQVG KRSTEARHGV RIDTSHRSLI LKCSSYRQAR 310 320 330 WWAQEITELA QGPGRDFLQL HRHDSYAPPR PGTLAR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human PLD2 and the analysis of PLD isoform splice variants." Steed P.M., Clark K.L., Boyar W.C., Lasala D.J. FASEB J. 12:1309-1317(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PLD2A; PLD2B AND PLD2C), CHARACTERIZATION, VARIANT CYS-172. Tissue: Brain.
[2]	"Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2." Lopez I., Arnold R.S., Lambeth J.D. J. Biol. Chem. 273:12846-12852(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PLD2A), CHARACTERIZATION, VARIANT ILE-577. Tissue: B-cell.
[3]	Saqib K.M., Clark J.M., Byrd P.J., Armstrong S.J., Wakelam M.J.O. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PLD2A AND PLD2B), VARIANTS GLY-632 AND SER-821.
[4]	"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] (ISOFORM PLD2A), VARIANTS CYS-172; ILE-577 AND GLY-632. Tissue: Skin and Uterus.
[5]	"Interaction of the type Ialpha PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4, 5-bisphosphate in the regulation of PLD2 activity." Divecha N., Roefs M., Halstead J.R., D'Andrea S., Fernandez-Borga M., Oomen L., Saqib K.M., Wakelam M.J.O., D'Santos C. EMBO J. 19:5440-5449(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIP5K1B.
[6]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-807.
+	Additional computationally mapped references.

Web resources

Wikipedia

Phospholipase D entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF033850 mRNA. Translation: AAD04197.1. AF035483 mRNA. Translation: AAC24498.1. AF038440 mRNA. Translation: AAB96655.1. AF038441 mRNA. Translation: AAB96656.1. BC015033 mRNA. Translation: AAH15033.1. BC056871 mRNA. Translation: AAH56871.1.
IPI	IPI00024727. IPI00216566. IPI00216567.
RefSeq	NP_001230037.1. NM_001243108.1. NP_002654.3. NM_002663.4.
UniGene	Hs.104519.
3D structure databases
ProteinModelPortal	O14939.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14939. 2 interactions.
MINT	MINT-141629.
STRING	9606.ENSP00000263088.
PTM databases
PhosphoSite	O14939.
Proteomic databases
PaxDb	O14939.
PRIDE	O14939.
Protocols and materials databases
DNASU	5338.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263088; ENSP00000263088; ENSG00000129219.
GeneID	5338.
KEGG	hsa:5338.
UCSC	uc002fzc.3. human. uc002fzd.3. human.
Organism-specific databases
CTD	5338.
GeneCards	GC17P004710.
H-InvDB	HIX0013451.
HGNC	HGNC:9068. PLD2.
HPA	HPA013397.
MIM	602384. gene.
neXtProt	NX_O14939.
PharmGKB	PA33397.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1502.
HOGENOM	HOG000246972.
HOVERGEN	HBG006650.
InParanoid	O14939.
KO	K01115.
OMA	DWRLDVM.
OrthoDB	EOG49ZXNK.
PhylomeDB	O14939.
Enzyme and pathway databases
BRENDA	3.1.4.4. 2681.
Pathway_Interaction_DB	alphasynuclein_pathway. Alpha-synuclein signaling. angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling. arf_3pathway. Arf1 pathway. arf6downstreampathway. Arf6 downstream pathway. arf6_traffickingpathway. Arf6 trafficking events. fcer1pathway. Fc-epsilon receptor I signaling in mast cells. lysophospholipid_pathway. LPA receptor mediated events.
Reactome	REACT_111217. Metabolism.
SignaLink	O14939.
Gene expression databases
ArrayExpress	O14939.
Bgee	O14939.
CleanEx	HS_PLD2.
Genevestigator	O14939.
GermOnline	ENSG00000129219. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit. 3.30.1520.10. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR001683. Phox. IPR025202. PLD-like_dom. IPR001849. Pleckstrin_homology. IPR001736. PLipase_D/transphosphatidylase. IPR016555. PLipase_D_euk. IPR015679. PLipase_D_fam. [Graphical view]
PANTHER	PTHR18896. PTHR18896. 1 hit.
Pfam	PF00614. PLDc. 1 hit. PF13091. PLDc_2. 1 hit. PF00787. PX. 1 hit. [Graphical view]
PIRSF	PIRSF009376. Phospholipase_D_euk. 1 hit.
SMART	SM00233. PH. 1 hit. SM00155. PLDc. 2 hits. SM00312. PX. 1 hit. [Graphical view]
SUPFAM	SSF64268. PX. 1 hit.
PROSITE	PS50003. PH_DOMAIN. False negative. PS50035. PLD. 2 hits. PS50195. PX. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O14939.
ChEMBL	CHEMBL2734.
DrugBank	DB00122. Choline.
GenomeRNAi	5338.
NextBio	20676.
SOURCE	Search...

Entry information

Entry name

PLD2_HUMAN

Accession

Primary (citable) accession number: O14939
Secondary accession number(s): O43540 , O43579, O43580, Q6PGR0, Q96BY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	February 21, 2001
Last modified:	May 29, 2013
This is version 127 of the entry and version 2 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.