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Protein

Phospholipase D3

Gene

PLD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probably involved in APP processing.1 Publication

Catalytic activityi

A phosphatidylcholine + H2O = choline + a phosphatidate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei201 – 2011PROSITE-ProRule annotation
Active sitei203 – 2031PROSITE-ProRule annotation
Active sitei208 – 2081PROSITE-ProRule annotation

GO - Molecular functioni

  • N-acylphosphatidylethanolamine-specific phospholipase D activity Source: UniProtKB-EC
  • phospholipase D activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid degradation, Lipid metabolism

Enzyme and pathway databases

ReactomeiR-HSA-1483148. Synthesis of PG.
R-HSA-2029485. Role of phospholipids in phagocytosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipase D3 (EC:3.1.4.4)
Short name:
PLD 3
Alternative name(s):
Choline phosphatase 3
HindIII K4L homolog
Hu-K4
Phosphatidylcholine-hydrolyzing phospholipase D3
Gene namesi
Name:PLD3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:17158. PLD3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3838CytoplasmicSequence analysisAdd
BLAST
Transmembranei39 – 5921Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini60 – 490431LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Alzheimer disease 19 (AD19)3 Publications
Disease susceptibility may be associated with variations affecting the gene represented in this entry. Disease association is, however, under debate. Some studies support PLD3 involvement in Alzheimer disease (PubMed:24336208, PubMed:25832410 and PubMed:25832409), while others do not (Ref.8, Ref.11 and Ref.12).6 Publications
Disease descriptionA late-onset form of Alzheimer disease, a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.
See also OMIM:615711
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti232 – 2321V → M in AD19; rare variant; unknown pathological significance. 2 Publications
VAR_071186

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Neurodegeneration

Organism-specific databases

MalaCardsiPLD3.
MIMi615711. phenotype.
PharmGKBiPA134887482.

Polymorphism and mutation databases

BioMutaiPLD3.
DMDMi74750647.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 490490Phospholipase D3PRO_0000280326Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi97 – 971N-linked (GlcNAc...)1 Publication
Glycosylationi132 – 1321N-linked (GlcNAc...)1 Publication

Post-translational modificationi

Glycosylated.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8IV08.
MaxQBiQ8IV08.
PaxDbiQ8IV08.
PRIDEiQ8IV08.
TopDownProteomicsiQ8IV08.

PTM databases

iPTMnetiQ8IV08.
PhosphoSiteiQ8IV08.

Expressioni

Tissue specificityi

Widely expressed. In the brain, high levels of expression are detected in the frontal, temporal and occipital cortices and hippocampus. Expressed at low level in corpus callosum.2 Publications

Gene expression databases

BgeeiQ8IV08.
CleanExiHS_PLD3.
ExpressionAtlasiQ8IV08. baseline and differential.
GenevisibleiQ8IV08. HS.

Organism-specific databases

HPAiCAB020812.
HPA012800.

Interactioni

Subunit structurei

Interacts with APP.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NFKB1P198382EBI-2689908,EBI-300010

Protein-protein interaction databases

BioGridi117173. 24 interactions.
IntActiQ8IV08. 12 interactions.
STRINGi9606.ENSP00000348901.

Structurei

3D structure databases

ProteinModelPortaliQ8IV08.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini196 – 22328PLD phosphodiesterase 1PROSITE-ProRule annotationAdd
BLAST
Domaini411 – 43727PLD phosphodiesterase 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the phospholipase D family.Curated
Contains 2 PLD phosphodiesterase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3603. Eukaryota.
ENOG410XQZ4. LUCA.
GeneTreeiENSGT00390000009798.
HOGENOMiHOG000293407.
HOVERGENiHBG052880.
InParanoidiQ8IV08.
KOiK16860.
OMAiGVYPDYT.
PhylomeDBiQ8IV08.
TreeFamiTF313378.

Family and domain databases

InterProiIPR032803. PLDc_3.
IPR001736. PLipase_D/transphosphatidylase.
[Graphical view]
PfamiPF00614. PLDc. 1 hit.
PF13918. PLDc_3. 1 hit.
[Graphical view]
SMARTiSM00155. PLDc. 2 hits.
[Graphical view]
PROSITEiPS50035. PLD. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8IV08-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKPKLMYQEL KVPAEEPANE LPMNEIEAWK AAEKKARWVL LVLILAVVGF
60 70 80 90 100
GALMTQLFLW EYGDLHLFGP NQRPAPCYDP CEAVLVESIP EGLDFPNAST
110 120 130 140 150
GNPSTSQAWL GLLAGAHSSL DIASFYWTLT NNDTHTQEPS AQQGEEVLRQ
160 170 180 190 200
LQTLAPKGVN VRIAVSKPSG PQPQADLQAL LQSGAQVRMV DMQKLTHGVL
210 220 230 240 250
HTKFWVVDQT HFYLGSANMD WRSLTQVKEL GVVMYNCSCL ARDLTKIFEA
260 270 280 290 300
YWFLGQAGSS IPSTWPRFYD TRYNQETPME ICLNGTPALA YLASAPPPLC
310 320 330 340 350
PSGRTPDLKA LLNVVDNARS FIYVAVMNYL PTLEFSHPHR FWPAIDDGLR
360 370 380 390 400
RATYERGVKV RLLISCWGHS EPSMRAFLLS LAALRDNHTH SDIQVKLFVV
410 420 430 440 450
PADEAQARIP YARVNHNKYM VTERATYIGT SNWSGNYFTE TAGTSLLVTQ
460 470 480 490
NGRGGLRSQL EAIFLRDWDS PYSHDLDTSA DSVGNACRLL
Length:490
Mass (Da):54,705
Last modified:March 1, 2003 - v1
Checksum:i444EC4D02F5610F1
GO

Sequence cautioni

The sequence AAB16799.1 differs from that shown. Reason: Frameshift at position 52. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti473 – 4731S → I in AAB16799 (PubMed:9140189).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti232 – 2321V → M in AD19; rare variant; unknown pathological significance. 2 Publications
VAR_071186

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U60644 mRNA. Translation: AAB16799.1. Frameshift.
BC000553 mRNA. Translation: AAH00553.2.
BC036327 mRNA. Translation: AAH36327.1.
BC096820 mRNA. Translation: AAH96820.1.
CCDSiCCDS33027.1.
RefSeqiNP_001026866.1. NM_001031696.3.
NP_001278240.1. NM_001291311.1.
NP_036400.2. NM_012268.3.
XP_005258761.1. XM_005258704.1.
XP_005258762.1. XM_005258705.2.
XP_005258764.1. XM_005258707.3.
XP_005258765.1. XM_005258708.2.
XP_005258766.1. XM_005258709.3.
XP_005258767.1. XM_005258710.3.
XP_006723185.1. XM_006723122.1.
XP_011524994.1. XM_011526692.1.
XP_011524995.1. XM_011526693.1.
UniGeneiHs.257008.

Genome annotation databases

EnsembliENST00000356508; ENSP00000348901; ENSG00000105223.
ENST00000409281; ENSP00000387022; ENSG00000105223.
ENST00000409419; ENSP00000386293; ENSG00000105223.
ENST00000409587; ENSP00000387050; ENSG00000105223.
ENST00000409735; ENSP00000386938; ENSG00000105223.
GeneIDi23646.
KEGGihsa:23646.
UCSCiuc002onj.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U60644 mRNA. Translation: AAB16799.1. Frameshift.
BC000553 mRNA. Translation: AAH00553.2.
BC036327 mRNA. Translation: AAH36327.1.
BC096820 mRNA. Translation: AAH96820.1.
CCDSiCCDS33027.1.
RefSeqiNP_001026866.1. NM_001031696.3.
NP_001278240.1. NM_001291311.1.
NP_036400.2. NM_012268.3.
XP_005258761.1. XM_005258704.1.
XP_005258762.1. XM_005258705.2.
XP_005258764.1. XM_005258707.3.
XP_005258765.1. XM_005258708.2.
XP_005258766.1. XM_005258709.3.
XP_005258767.1. XM_005258710.3.
XP_006723185.1. XM_006723122.1.
XP_011524994.1. XM_011526692.1.
XP_011524995.1. XM_011526693.1.
UniGeneiHs.257008.

3D structure databases

ProteinModelPortaliQ8IV08.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117173. 24 interactions.
IntActiQ8IV08. 12 interactions.
STRINGi9606.ENSP00000348901.

PTM databases

iPTMnetiQ8IV08.
PhosphoSiteiQ8IV08.

Polymorphism and mutation databases

BioMutaiPLD3.
DMDMi74750647.

Proteomic databases

EPDiQ8IV08.
MaxQBiQ8IV08.
PaxDbiQ8IV08.
PRIDEiQ8IV08.
TopDownProteomicsiQ8IV08.

Protocols and materials databases

DNASUi23646.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356508; ENSP00000348901; ENSG00000105223.
ENST00000409281; ENSP00000387022; ENSG00000105223.
ENST00000409419; ENSP00000386293; ENSG00000105223.
ENST00000409587; ENSP00000387050; ENSG00000105223.
ENST00000409735; ENSP00000386938; ENSG00000105223.
GeneIDi23646.
KEGGihsa:23646.
UCSCiuc002onj.5. human.

Organism-specific databases

CTDi23646.
GeneCardsiPLD3.
HGNCiHGNC:17158. PLD3.
HPAiCAB020812.
HPA012800.
MalaCardsiPLD3.
MIMi615698. gene.
615711. phenotype.
neXtProtiNX_Q8IV08.
PharmGKBiPA134887482.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3603. Eukaryota.
ENOG410XQZ4. LUCA.
GeneTreeiENSGT00390000009798.
HOGENOMiHOG000293407.
HOVERGENiHBG052880.
InParanoidiQ8IV08.
KOiK16860.
OMAiGVYPDYT.
PhylomeDBiQ8IV08.
TreeFamiTF313378.

Enzyme and pathway databases

ReactomeiR-HSA-1483148. Synthesis of PG.
R-HSA-2029485. Role of phospholipids in phagocytosis.

Miscellaneous databases

ChiTaRSiPLD3. human.
GenomeRNAii23646.
PROiQ8IV08.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IV08.
CleanExiHS_PLD3.
ExpressionAtlasiQ8IV08. baseline and differential.
GenevisibleiQ8IV08. HS.

Family and domain databases

InterProiIPR032803. PLDc_3.
IPR001736. PLipase_D/transphosphatidylase.
[Graphical view]
PfamiPF00614. PLDc. 1 hit.
PF13918. PLDc_3. 1 hit.
[Graphical view]
SMARTiSM00155. PLDc. 2 hits.
[Graphical view]
PROSITEiPS50035. PLD. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A human homolog of the vaccinia virus HindIII K4L gene is a member of the phospholipase D superfamily."
    Cao J.X., Koop B.F., Upton C.
    Virus Res. 48:11-18(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Mammary gland.
  2. "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].
    Tissue: Brain, Colon and Lung.
  3. "Hu-K4 is a ubiquitously expressed type 2 transmembrane protein associated with the endoplasmic reticulum."
    Munck A., Boehm C., Seibel N.M., Hashemol Hosseini Z., Hampe W.
    FEBS J. 272:1718-1726(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, GLYCOSYLATION.
  4. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-97 AND ASN-132.
    Tissue: Liver.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  7. "Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease."
    UK Brain Expression Consortium
    Cruchaga C., Karch C.M., Jin S.C., Benitez B.A., Cai Y., Guerreiro R., Harari O., Norton J., Budde J., Bertelsen S., Jeng A.T., Cooper B., Skorupa T., Carrell D., Levitch D., Hsu S., Choi J., Ryten M.
    , Hardy J., Ryten M., Trabzuni D., Weale M.E., Ramasamy A., Smith C., Sassi C., Bras J., Gibbs J.R., Hernandez D.G., Lupton M.K., Powell J., Forabosco P., Ridge P.G., Corcoran C.D., Tschanz J.T., Norton M.C., Munger R.G., Schmutz C., Leary M., Demirci F.Y., Bamne M.N., Wang X., Lopez O.L., Ganguli M., Medway C., Turton J., Lord J., Braae A., Barber I., Brown K., Passmore P., Craig D., Johnston J., McGuinness B., Todd S., Heun R., Kolsch H., Kehoe P.G., Hooper N.M., Vardy E.R., Mann D.M., Pickering-Brown S., Brown K., Kalsheker N., Lowe J., Morgan K., David Smith A., Wilcock G., Warden D., Holmes C., Pastor P., Lorenzo-Betancor O., Brkanac Z., Scott E., Topol E., Morgan K., Rogaeva E., Singleton A.B., Hardy J., Kamboh M.I., St George-Hyslop P., Cairns N., Morris J.C., Kauwe J.S., Goate A.M.
    Nature 505:550-554(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, POSSIBLE INVOLVEMENT IN AD19, VARIANT AD19 MET-232, TISSUE SPECIFICITY, INTERACTION WITH APP.
  8. Cited for: LACK OF INVOLVEMENT IN AD19.
  9. Cited for: POSSIBLE INVOLVEMENT IN AD19.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. Cited for: LACK OF ASSOCIATION OF VARIANT AD19 MET-232 WITH ALZHEIMER DISEASE.
  12. Cited for: LACK OF INVOLVEMENT IN AD19.
  13. Cited for: POSSIBLE INVOLVEMENT IN AD19.

Entry informationi

Entry nameiPLD3_HUMAN
AccessioniPrimary (citable) accession number: Q8IV08
Secondary accession number(s): Q92853, Q9BW87
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 1, 2003
Last modified: June 8, 2016
This is version 118 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 19
    Human chromosome 19: 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.