Phospholipase D2 - Homo sapiens (Human)

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
    Phosphatidylcholine-hydrolyzing phospholipase D2
    PLD1C

Gene names

Name:

PLD2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	933 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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 PIP5K1A.
Subcellular location	Membrane; Peripheral membrane protein By similarity.
Tissue specificity	Ubiquitous.
Sequence similarities	Belongs to the phospholipase D family. Contains 1 PH domain. Contains 2 PLD phosphodiesterase domains. Contains 1 PX (phox homology) domain.

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Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Molecular function	Hydrolase
Gene Ontology (GO)
Biological process	cytoskeleton organization Traceable author statement. Source: ProtInc lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW small GTPase mediated signal transduction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	NAPE-specific phospholipase D activity Inferred from electronic annotation. Source: EC phosphoinositide binding Inferred from electronic annotation. Source: InterPro phospholipase D activity Ref.2 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	2	EBI-1053996,EBI-401755

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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.

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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: dbSNP rs2286672. Ref.1 Ref.4

VAR_051704

Natural variant

577

1

T → I: dbSNP rs1052748. Ref.4 Ref.2

VAR_051705

Natural variant

804

1

A → T: dbSNP rs11545163.

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: dbSNP rs3764897.

VAR_051707

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

632

1

E → G in AAB96656. Ref.3

Sequence conflict

784

1

D → G in AAB96656. Ref.3

Sequence conflict

801 – 802

2

MN → ID in AAC24498. Ref.2

Sequence conflict

821

1

G → S in AAB96655. Ref.3

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Sequences

Sequence		Length	Mass (Da)
Isoform PLD2A [UniParc]. Last modified February 21, 2001. Version 2. Checksum: F25F6B73B45F57ED Show »	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 « Hide
Isoform PLD2B. Checksum: 6E0D388D73E222AF Show »	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 « Hide
Isoform PLD2C. Checksum: B88330C3765169E3 Show »	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 « Hide

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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: 9761774] [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: 9582313] [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).
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PLD2A), VARIANTS CYS-172 AND ILE-577. Tissue: 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: 11032811] [Abstract] Cited for: INTERACTION WITH PIP5K1A.
[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. Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-807.
+	Additional computationally mapped references.

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Web resources

Wikipedia

Phospholipase D entry

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Cross-references

Sequence databases
	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.
IPI	IPI00024727. IPI00216566. IPI00216567.
RefSeq	NP_002654.3.
UniGene	Hs.104519
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O14939. 6 interactions.
PTM databases
PhosphoSite	O14939.
Proteomic databases
PRIDE	O14939.
Genome annotation databases
Ensembl	ENSG00000129219. Homo sapiens. [Contig view]
GeneID	5338.
KEGG	hsa:5338.
Organism-specific databases
GeneCards	GC17P004657.
H-InvDB	HIX0013451.
HGNC	HGNC:9068. PLD2.
HPA	HPA013397.
MIM	602384. gene.
PharmGKB	PA142672077.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O14939.
HOVERGEN	O14939.
OMA	O14939. WRLDKIL.
Enzyme and pathway databases
BRENDA	3.1.4.4. 247.
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.
Gene expression databases
ArrayExpress	O14939.
Bgee	O14939.
CleanEx	HS_PLD2.
GermOnline	ENSG00000129219. Homo sapiens.
Family and domain databases
InterPro	IPR015679. Phospholipase_D. IPR001849. Pleckstrin_homology. IPR001736. PLipase_D/transphosphatidylase. IPR016555. PLipase_D_euk. IPR001683. PX. [Graphical view]
Gene3D	G3DSA:3.30.1520.10. PX. 1 hit.
PANTHER	PTHR18896. Phospholipase_D. 1 hit.
Pfam	PF00169. PH. 1 hit. PF00614. PLDc. 2 hits. 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]
PROSITE	PS50003. PH_DOMAIN. False negative. PS50035. PLD. 2 hits. PS50195. PX. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00122. Choline.
NextBio	20676.
SOURCE	Search...

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Entry information

Entry name

PLD2_HUMAN

Accession

Primary (citable) accession number: O14939
Secondary accession number(s): O43540

Q96BY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	February 21, 2001
Last modified:	June 16, 2009
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

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

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

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents