Affinage

PLAA

Phospholipase A-2-activating protein · UniProt Q9Y263

Length
795 aa
Mass
87.2 kDa
Annotated
2026-04-28
95 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLAA is a ubiquitin-adaptor protein that bridges the AAA-ATPase p97/VCP to ubiquitinated substrates across multiple quality-control and trafficking pathways, including endolysosomal damage clearance, mitochondria-associated degradation, DNA-damage ubiquitin homeostasis, and multivesicular body sorting. Its C-terminal PUL (Armadillo-repeat) domain binds the p97 C-terminus through a positively charged ridge that buries p97-Tyr805, while its PFU domain independently engages ubiquitin and the endosomal sorting factor Hse1/STAM (PMID:19887378, PMID:18508771). At damaged lysosomes, PLAA cooperates with UBXD1 and the deubiquitinase YOD1 to selectively remove K48-linked ubiquitin, enabling K63-ubiquitin/p62-dependent autophagic clearance; at synapses, loss-of-function mutations cause K63-polyubiquitin accumulation, impaired vesicle recycling, and neurodevelopmental disease in humans and mice (PMID:27753622, PMID:28413018). PLAA also regulates mRNA processing bodies through a distinct intrinsically disordered region that recruits the decapping-complex subunit DCAP-1, a function separable from its ubiquitin-dependent roles (PMID:40560612).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1989 Low

    The earliest biochemical activity attributed to PLAA was direct activation of low-molecular-weight PLA2, establishing it as a potential modulator of phospholipid metabolism, though the mechanism was unclear.

    Evidence In vitro enzyme assay with purified PLAP and PLA2 isoforms from human synovial fluid

    PMID:8431486

    Open questions at the time
    • No mutagenesis or structural validation of the activator–enzyme interaction
    • Relationship to PLAA's ubiquitin-binding functions unresolved
    • Activation mechanism (direct vs. indirect) not distinguished
  2. 1999 Low

    PLAP peptide was shown to stimulate Golgi membrane tubulation through PLA2 activation, linking PLAA to retrograde membrane trafficking, but only through pharmacological reconstitution.

    Evidence Cell-free Golgi tubulation assay and permeabilized cell system with PLA2 antagonist pharmacology

    PMID:10440936

    Open questions at the time
    • Relies on exogenous peptide without genetic loss-of-function
    • No identification of the specific PLA2 isoform involved in cells
    • Relationship to PLAA's p97-binding functions unknown
  3. 2005 Medium

    PLAA peptide recapitulated 1α,25(OH)₂D₃ rapid signaling in chondrocytes—activating PLA2, PKCα, and PLC—establishing PLAA as an effector in non-genomic vitamin D signaling upstream of arachidonic acid release.

    Evidence Peptide addition to chondrocyte cultures with PLA2, PKC isoform, and PLC activity assays plus inhibitor pharmacology

    PMID:15368540

    Open questions at the time
    • Relies on exogenous peptide rather than genetic ablation
    • Direct physical interaction between PLAA and the vitamin D membrane receptor not structurally resolved
  4. 2006 Medium

    Using the yeast ortholog Doa1, PLAA was placed in ubiquitin homeostasis: Doa1 loss abolished damage-induced PCNA monoubiquitination and reduced H2B ubiquitination, revealing both ubiquitin-supply and substrate-specific functions in the DNA damage response.

    Evidence Yeast doa1Δ mutant with ubiquitin immunoblotting, overexpression rescue, and epistasis with RAD6/RAD18/BRE1

    PMID:16705165

    Open questions at the time
    • H2B ubiquitination defect not rescued by ubiquitin overexpression—mechanism unknown
    • Not tested in mammalian cells
  5. 2008 High

    The PFU domain was shown to bind the endosomal sorting factor Hse1/STAM independently of ubiquitin binding, placing PLAA directly in the MVB sorting pathway—a function distinct from its ubiquitin-supply role.

    Evidence Direct pulldown, site-directed mutagenesis separating Hse1-binding from ubiquitin-binding residues, GFP-Cps1 cargo missorting, and genetic epistasis with vps27Δ in yeast

    PMID:18508771

    Open questions at the time
    • Mammalian STAM–PLAA interaction not validated
    • Structural basis of PFU–SH3 interaction not yet determined at this time
  6. 2009 High

    The crystal structure of the PUL domain bound to the p97 C-terminal peptide revealed the Armadillo-repeat architecture and the critical p97-Tyr805 burial, and mutagenesis proved this interface is functionally required for a subset of ubiquitin-pathway processes.

    Evidence X-ray crystallography of PUL–p97 complex; Doa1 PUL point mutants with in vivo complementation in yeast

    PMID:19887378

    Open questions at the time
    • Full-length PLAA–p97 hexamer complex structure not resolved
    • Which mammalian p97-dependent processes specifically require the PUL interface was not tested
  7. 2014 Medium

    Quantitative biophysics (ITC, SAXS) of the PFU–Hse1/SH3 interaction defined ~5 µM affinity and identified critical residues (Doa1-Asn438, Hse1-Trp254), separating this interface from ubiquitin binding at Phe434.

    Evidence ITC affinity measurement, SAXS molecular envelope, site-directed mutagenesis in yeast

    PMID:24607902

    Open questions at the time
    • Solution structure from SAXS is low-resolution compared to crystallography
    • Functional consequence of affinity perturbation not tested in vivo
  8. 2016 High

    Two studies established PLAA as a p97 cofactor in organelle-specific quality control: (1) at damaged lysosomes, PLAA/UBXD1/YOD1 selectively remove K48-ubiquitin to license autophagic clearance; (2) at mitochondria, Doa1/PLAA recruits ubiquitinated outer-membrane substrates to Cdc48 for mitochondria-associated degradation.

    Evidence siRNA knockdown, ubiquitin-linkage antibodies, lysosomal damage assay in mammalian cells (ELDR); genetic screen, Co-IP with ubiquitinated mitochondrial substrates, oxidative stress survival in yeast (MAD)

    PMID:27044889 PMID:27753622

    Open questions at the time
    • Structural basis for PLAA selectivity toward K48- vs K63-ubiquitin chains not determined
    • Whether PLAA functions in MAD in mammalian cells not tested
  9. 2017 High

    Biallelic PLAA mutations in humans caused progressive neurodegeneration with K63-polyubiquitin accumulation and impaired synaptic vesicle recycling, establishing PLAA as essential for ubiquitin-dependent endolysosomal degradation at the synapse and linking it to Mendelian neurodevelopmental disease.

    Evidence Human patient genetics plus hypomorphic mouse Plaa mutant with electrophysiology, ubiquitin-conjugate profiling, and synaptic vesicle assays

    PMID:28413018

    Open questions at the time
    • Precise synaptic substrates whose accumulation drives pathology not identified
    • Whether disease mechanism is p97-dependent or involves PLAA's other interactions not resolved
  10. 2022 Medium

    In ovarian cancer cells, PLAA was shown to promote ubiquitin-mediated degradation of METTL3, thereby reducing m6A modification and stability of TRPC3 mRNA and suppressing metastasis—linking PLAA's ubiquitin-adaptor function to epitranscriptomic regulation.

    Evidence PLAA knockdown/overexpression, ubiquitination assays, m6A-seq, TRPC3 stability assay, orthotopic xenograft model

    PMID:35869392

    Open questions at the time
    • Whether PLAA promotes METTL3 degradation via p97 not tested
    • Generalizability beyond ovarian cancer unknown
  11. 2024 Medium

    De novo PUL-domain missense variants in children with autism and intellectual disability were shown to reduce PLAA–p97 binding in vitro, extending the disease spectrum and confirming that the p97 interaction is critical for neurodevelopment.

    Evidence Exome sequencing, computational structural modeling, in vitro PLAA–p97 binding assay with mutant proteins

    PMID:38650658

    Open questions at the time
    • No cellular or animal model validation of these specific variants
    • Whether variants also affect other PLAA interactions (e.g., PFU-mediated) not assessed
  12. 2025 Medium

    A previously unrecognized function was uncovered: PLAA's intrinsically disordered region recruits the mRNA decapping factor DCAP-1 to P-bodies, a role entirely separable from its PFU/PUL-dependent ubiquitin-trafficking functions, revealing that PLAA regulates the proteome through both protein degradation and mRNA regulation.

    Evidence Proteome-scale mass spectrometry, direct pulldown of UFD-3–DCAP-1, P-body imaging, IDR deletion mutants, and MVB sorting assays in C. elegans

    PMID:40560612

    Open questions at the time
    • Mammalian PLAA–DCP1 interaction not validated
    • Whether IDR-mediated P-body function is conserved in vertebrates unknown
    • Mechanism by which IDR recruits DCAP-1 (direct binding surface) not structurally defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how PLAA distinguishes K48- from K63-linked ubiquitin chains at damaged organelles; (2) whether the PLA2-activating and p97-adaptor functions operate in the same or distinct physiological contexts; (3) the identity of critical synaptic substrates whose accumulation drives neurodegeneration; and (4) whether PLAA's P-body regulatory function via its IDR is conserved in mammals.
  • No ubiquitin-chain selectivity mechanism defined
  • PLA2 activation vs. p97 adaptor function relationship unresolved
  • Full-length PLAA structure lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005764 lysosome 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-73894 DNA Repair 2 R-HSA-8953854 Metabolism of RNA 1 R-HSA-9612973 Autophagy 1
Partners
DCAP1METTL3PDIA3STAMUBXD1VCPYOD1
Complex memberships
Cdc48-Ufd1-Npl4-Doa1 complexWss1-Cdc48-Doa1 ternary complexp97/VCP-PLAA-UBXD1-YOD1 (ELDR complex)

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 The C-terminal PUL domain of PLAA forms a 6-mer Armadillo-containing domain whose N-terminal extension folds back to create a positively charged ridge that binds the C-terminus of p97/VCP (specifically burying p97-Tyr805). Crystal structure of the PUL domain–p97 C-terminal peptide complex was solved at high resolution, and point mutations in the yeast ortholog Doa1 that disrupt this interface reduce ubiquitin levels and cause subset-specific growth phenotypes, demonstrating that the p97–PLAA physical interaction is functionally important for a subset of PLAA-dependent ubiquitin-pathway processes. X-ray crystallography of PUL–p97 complex; site-directed mutagenesis of Doa1 PUL domain; in vivo complementation in doa1Δ yeast The Journal of biological chemistry High 19887378
2016 Upon lysosomal rupture, p97/VCP translocates to damaged lysosomes and cooperates with PLAA, UBXD1, and the deubiquitinase YOD1 (collectively termed ELDR components) to selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes, thereby promoting autophagosome formation downstream of K63-linked ubiquitination and p62 recruitment. Loss of p97 or these cofactors impairs clearance of ruptured lysosomes by autophagy. SiRNA knockdown, co-immunoprecipitation, ubiquitin-linkage–specific antibodies, lysosomal damage assays, MEF p97 mutant model, patient tissue analysis The EMBO journal High 27753622
2017 Hypomorphic mutations in PLAA (ubiquitin adaptor protein) in both humans and mice cause accumulation of K63-polyubiquitylated proteins and synaptic membrane proteins due to perturbed endolysosomal degradation, disrupting synaptic vesicle recycling and neurotransmission. This establishes PLAA as an essential mediator of ubiquitin-mediated endolysosomal trafficking at the synapse. Human genetics (biallelic PLAA mutations), mouse hypomorphic Plaa mutant neurons, biochemical analysis of ubiquitin conjugates, electrophysiology of synaptic vesicle recycling American journal of human genetics High 28413018
2008 Doa1/PLAA's PFU domain directly binds the SH3 domain of Hse1 (STAM homolog in yeast) with an affinity that is independent of ubiquitin binding. Mutations in Doa1 that block Hse1 binding without affecting ubiquitin binding cause missorting of the MVB cargo GFP-Cps1 and a synthetic growth defect with loss of Vps27, placing Doa1 in the endosomal sorting/MVB pathway. Direct binding assay (pulldown), site-directed mutagenesis of Doa1, GFP-cargo missorting assay, genetic epistasis (doa1Δ vps27Δ double mutant), ubiquitin overexpression suppression test The Journal of biological chemistry High 18508771
2010 Crystal structure of the PFU–PUL domain pair of yeast Doa1/Ufd3 (PLAA ortholog) at 1.9 Å revealed that the PUL domain adopts an Armadillo-like repeat structure with a positively charged concave surface that binds the negatively charged C-terminal region of Cdc48/p97, and that the PFU domain surface is implicated in binding ubiquitin and Hse1. X-ray crystallography; surface electrostatic analysis; structural comparison with Ufd2 The Kobe journal of medical sciences Medium 21063153
2015 Wss1 metalloprotease forms a SUMO-specific ternary complex with the AAA ATPase Cdc48 and Doa1/PLAA as adaptor upon genotoxic stress. Doa1 serves as the adaptor bridging Wss1 to Cdc48 for processing sumoylated chromatin-bound proteins and clearing covalent topoisomerase complexes. Co-immunoprecipitation, yeast genetics (suppressor analysis), in vivo UV/camptothecin survival assays, biochemical reconstitution of the ternary complex eLife Medium 26349035
2006 Doa1/PLAA (yeast ortholog) controls ubiquitin availability for the DNA damage response: in doa1Δ cells, damage-induced PCNA monoubiquitination is abolished and histone H2B ubiquitination is severely reduced. Ubiquitin overexpression rescues PCNA ubiquitination but not H2B ubiquitination, indicating that Doa1 both supplies ubiquitin (from the proteasomal pathway) and plays a more specific role in H2B monoubiquitination during DNA damage. Yeast genetic interaction screen, ubiquitin immunoblotting, ubiquitin overexpression suppression, epistasis with RAD6, RAD18, BRE1, UBP8/UBP10 Molecular and cellular biology Medium 16705165
2016 Doa1/PLAA (yeast ortholog) functions as a substrate-recruiting adaptor for the Cdc48-Ufd1-Npl4 complex specifically in mitochondria-associated degradation (MAD): Doa1 interacts with ubiquitinated outer-membrane substrates and facilitates their recruitment to Cdc48, and is critical for cell survival under mitochondrial oxidative stress but dispensable under ER stress. Genetic screen (MAD pathway), substrate accumulation assays, co-immunoprecipitation of Doa1 with ubiquitinated substrates and Cdc48, deletion analysis, oxidative stress survival The Journal of cell biology Medium 27044889
2014 PLAA (via its molecular interaction with Pdia3 membrane receptor) and caveolae are required for rapid 1α,25(OH)2D3-mediated activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in growth plate chondrocytes. Immunoprecipitation showed increased CaM binding to PLAA in response to 1α,25(OH)2D3, placing PLAA upstream of CaMKII in this non-genomic vitamin D signaling cascade. Antibody blocking of PLAA or Pdia3, PLAA peptide stimulation, caveolae disruption (methyl-β-cyclodextrin), co-immunoprecipitation (CaM–PLAA), CaMKII activity assay Connective tissue research Medium 25158196
2005 PLAA is required for 1α,25(OH)2D3 rapid membrane-mediated signaling in growth plate chondrocytes: PLAA peptide increases arachidonic acid release, PLA2 activity, PKCα (but not other PKC isoforms), phospholipase C-β1/β3 activity, alkaline phosphatase, and proteoglycan production comparable to 1α,25(OH)2D3. PLA2 inhibitors and cyclooxygenase inhibitors block PLAA peptide effects on PKC, indicating arachidonic acid and its metabolites (via EP1 prostaglandin receptor) mediate downstream signaling. PLAA peptide addition to chondrocyte cultures, PLA2 activity assay, PKC isoform-specific assays, PLC activity assay, inhibitor pharmacology (quinacrine, AACOCF3, indomethacin, SC19220, AH6809), [3H]-thymidine incorporation Journal of cellular physiology Medium 15368540
2009 PLAA overexpression enhances cisplatin-induced apoptosis in HeLa cells through four pathways: (1) accumulation of arachidonic acid and mitochondrial damage (cytochrome c release); (2) downregulation of cytoprotective clusterin; (3) upregulation of pro-apoptotic IL-32; and (4) activation of JNK/c-Jun signaling and FasL expression. siRNA knockdown of PLAA reduces cisplatin-induced DNA fragmentation and PLA2 activation, confirming that these effects are PLAA-dependent. Tet-off PLAA overexpression system, siRNA knockdown, caspase activity assays, cytochrome c leakage, PLA2 activity, proteomics (phospho-JNK/c-Jun), exogenous arachidonic acid rescue Cellular signalling Medium 19258036
2008 PLAA overexpression (plaa-high HeLa cells) enhances TNF-α-induced activation of cytosolic PLA2, COX-2, and NF-κB, leading to increased PGE2 and IL-6 production. Sp1 transcription factor binds a stimulatory element in exon 1 of the plaa gene and maintains its basal expression, as demonstrated by luciferase reporter assay and competitive decoy oligonucleotide binding. Tet-off overexpression, ELISA (PGE2, IL-6), microarray with functional follow-up, luciferase reporter assay, Sp1 decoy oligonucleotides, competitive binding assay Cellular signalling Medium 18291623
2022 PLAA inhibits ovarian cancer metastasis by promoting ubiquitin-mediated degradation of METTL3, thereby reducing METTL3-dependent m6A modification of TRPC3 mRNA. Reduced TRPC3 mRNA stability lowers TRPC3 protein and intracellular Ca2+ levels, suppressing cancer cell migration and invasion. PLAA knockdown/overexpression in cell lines, orthotopic xenograft mouse model, ubiquitination assays, METTL3 m6A-seq, TRPC3 mRNA stability assay, Ca2+ imaging Oncogene Medium 35869392
2024 De novo missense variants in the PUL domain of PLAA found in children with neurodevelopmental disorders (autism, intellectual disability) reduce PLAA–p97/VCP interaction as shown by in vitro binding assays, and computational modeling reveals abnormal C-terminal chain arrangements, establishing that disruption of PLAA–p97 interaction and consequent perturbed vesicle recycling underlies these NDDs. Exome/genome sequencing, computational structural modeling, in vitro PLAA–p97 interaction assay with mutant proteins Frontiers in molecular neuroscience Medium 38650658
2014 Yeast Doa1/PLAA PFU domain interacts with the SH3 domain of Hse1 with ~5 µM affinity; Asn-438 of Doa1/PFU and Trp-254 of Hse1/SH3 are critical for the interaction (hydrogen bonding is the major determinant), while Phe-434 (ubiquitin-binding residue) is not required. Solution structure of the PFU:SH3 complex was determined by SAXS combined with molecular docking. Isothermal titration calorimetry, site-directed mutagenesis, small-angle X-ray scattering, molecular docking Biochemical and biophysical research communications Medium 24607902
1999 PLAP peptide (PLAPp, a PLA2-activating protein peptide) stimulates cytosol-dependent Golgi membrane tubulation in a saturable, dose-dependent manner in vitro and in permeabilized cells, and this stimulation is blocked by cytosolic PLA2 antagonists including the Ca2+-independent PLA2-specific inhibitor bromoenol lactone. The effect is reproduced in a permeabilized cell system reconstituting Golgi-to-ER retrograde trafficking, linking PLA2 activation by PLAP to Golgi tubule formation and retrograde membrane trafficking. Cell-free Golgi tubulation reconstitution assay, permeabilized cell system, PLA2 antagonist pharmacology (bromoenol lactone, other inhibitors) Journal of cellular biochemistry Low 10440936
1989 PLAP (phospholipase A2-activating protein) isolated from human rheumatoid synovial fluid and from neutrophils activates purified low-molecular-weight (~14 kDa) PLA2 more than 20-fold at a protein-to-phospholipid ratio of 1:10^6, while having no effect on a high-molecular-weight (~110 kDa) PLA2, suggesting a direct enzyme–activator interaction rather than membrane perturbation as the mechanism of stimulation. PLA2 purification; in vitro enzyme activity assay with purified PLAP and purified PLA2 isoforms; comparison with melittin Biochimica et biophysica acta Low 8431486
2025 C. elegans PLAA ortholog UFD-3 directly interacts with the mRNA decapping complex regulatory subunit DCAP-1, and UFD-3's intrinsic disordered region (IDR) is required for recruiting DCAP-1 to P-bodies. Loss of the IDR does not affect UFD-3's role in sorting ubiquitinated proteins through the MVB pathway, demonstrating that PLAA/UFD-3 regulates the proteome via two distinct pathways: ubiquitin-dependent protein degradation and mRNA regulation through P-bodies. Proteome-scale interactomics (mass spectrometry), direct biochemical interaction assay (UFD-3–DCAP-1 pulldown), fluorescence imaging of P-bodies in C. elegans, IDR deletion mutant analysis, MVB sorting assay Proceedings of the National Academy of Sciences of the United States of America Medium 40560612

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. The EMBO journal 284 27753622
2007 PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization. The Journal of biological chemistry 160 17522060
2007 Weissellicin 110, a newly discovered bacteriocin from Weissella cibaria 110, isolated from plaa-som, a fermented fish product from Thailand. Applied and environmental microbiology 78 17293526
2005 OCT4 immunohistochemistry is superior to placental alkaline phosphatase (PLAP) in the diagnosis of central nervous system germinoma. The American journal of surgical pathology 78 15725806
2000 Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome. Human pathology 78 11014571
2016 Doa1 targets ubiquitinated substrates for mitochondria-associated degradation. The Journal of cell biology 75 27044889
2007 Expression of the mucus adhesion genes Mub and MapA, adhesion-like factor EF-Tu and bacteriocin gene plaA of Lactobacillus plantarum 423, monitored with real-time PCR. International journal of food microbiology 71 17399831
2015 Wss1 metalloprotease partners with Cdc48/Doa1 in processing genotoxic SUMO conjugates. eLife 66 26349035
1989 A phospholipase A2-activating protein (PLAP) stimulates human neutrophil aggregation and release of lysosomal enzymes, superoxide, and eicosanoids. Journal of immunology (Baltimore, Md. : 1950) 53 2541202
2008 PLAP-1/asporin inhibits activation of BMP receptor via its leucine-rich repeat motif. Biochemical and biophysical research communications 49 18407830
2012 miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells. Molecular medicine reports 48 22367347
2002 Fermentation and microflora of plaa-som, a thai fermented fish product prepared with different salt concentrations. International journal of food microbiology 46 11883675
2008 DOA1/UFD3 plays a role in sorting ubiquitinated membrane proteins into multivesicular bodies. The Journal of biological chemistry 40 18508771
2017 PLAA Mutations Cause a Lethal Infantile Epileptic Encephalopathy by Disrupting Ubiquitin-Mediated Endolysosomal Degradation of Synaptic Proteins. American journal of human genetics 37 28413018
2006 Diagnostic value of markers M2A, OCT3/4, AP-2gamma, PLAP and c-KIT in the detection of extragonadal seminomas. Histopathology 37 16918976
1993 Responses of purified phospholipases A2 to phospholipase A2 activating protein (PLAP) and melittin. Biochimica et biophysica acta 37 8431486
2006 Regulation of PLAP-1 expression in periodontal ligament cells. Journal of dental research 35 16632759
1990 The expression of placental alkaline phosphatase (PLAP) and PLAP-like enzymes in normal and neoplastic human tissues. An immunohistological survey using monoclonal antibodies. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 35 2171580
2009 Structure and function of the PLAA/Ufd3-p97/Cdc48 complex. The Journal of biological chemistry 34 19887378
2006 Role of Doa1 in the Saccharomyces cerevisiae DNA damage response. Molecular and cellular biology 33 16705165
2022 PLAA suppresses ovarian cancer metastasis via METTL3-mediated m6A modification of TRPC3 mRNA. Oncogene 31 35869392
2015 PLAP-1/Asporin Regulates TLR2- and TLR4-induced Inflammatory Responses. Journal of dental research 30 26399972
2005 Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia. Gynecologic oncology 30 15907336
2005 Phospholipase A2 activating protein (PLAA) is required for 1alpha,25(OH)2D3 signaling in growth plate chondrocytes. Journal of cellular physiology 29 15368540
2021 Pattern of placental alkaline phosphatase (PLAP) expression in human tumors: a tissue microarray study on 12,381 tumors. The journal of pathology. Clinical research 28 34363325
2013 Putrescine importer PlaP contributes to swarming motility and urothelial cell invasion in Proteus mirabilis. The Journal of biological chemistry 26 23572531
2010 Identification of lactic acid bacteria associated with the production of plaa-som, a traditional fermented fish product of Thailand. International journal of food microbiology 26 20167386
1989 Serum placental-like alkaline phosphatase (PLAP): a novel combined enzyme linked immunoassay for monitoring ovarian cancer. Journal of clinical pathology 26 2921344
2014 Inhibitory effects of PLAP-1/asporin on periodontal ligament cells. Journal of dental research 25 24453179
2009 Phospholipase A2-activating protein (PLAA) enhances cisplatin-induced apoptosis in HeLa cells. Cellular signalling 25 19258036
2006 A novel role for placental leucine aminopeptidase (P-LAP) as a determinant of chemoresistance in endometrial carcinoma cells. International journal of cancer 25 16187279
1999 HLA DOA1 and DOB1 loci in Honduran women with cervical dysplasia and invasive cervical carcinoma and their relationship to human papillomavirus infection. Human biology 25 10380373
2015 PLAP-1/Asporin Positively Regulates FGF-2 Activity. Journal of dental research 23 26239644
2022 Plap-1 lineage tracing and single-cell transcriptomics reveal cellular dynamics in the periodontal ligament. Development (Cambridge, England) 22 36245218
2020 PLAP -CAR T cells mediate high specific cytotoxicity against colon cancer cells. Frontiers in bioscience (Landmark edition) 21 32472757
1999 Stimulation of Golgi membrane tubulation and retrograde trafficking to the ER by phospholipase A(2) activating protein (PLAP) peptide. Journal of cellular biochemistry 21 10440936
1987 RFLP of the human placental alkaline phosphatase gene (PLAP). Nucleic acids research 21 2891112
2008 Alteration in the activation state of new inflammation-associated targets by phospholipase A2-activating protein (PLAA). Cellular signalling 19 18291623
1987 Catalytic and immunologic activities of placental-like alkaline phosphatase in clinical studies. The value of PLAP in follow-up of ovarian cancer. Clinica chimica acta; international journal of clinical chemistry 18 2443278
2010 Immunohistochemical expression analysis of Cx43, Cx26, c-KIT and PlAP in contralateral testis biopsies of patients with non-seminomatous testicular germ cell tumor. Histochemistry and cell biology 17 21161545
2021 LncRNA DCST1-AS1 inhibits PDLCs' proliferation in periodontitis and may bind with miR-21 precursor to upregulate PLAP-1. Journal of periodontal research 16 33533513
2015 Analysis of POU5F1, c-Kit, PLAP, AP2γ and SALL4 in gonocytes of patients with cryptorchidism. Acta histochemica 16 26315991
1999 Transgenic mice ubiquitously expressing human placental alkaline phosphatase (PLAP): an additional reporter gene for use in tandem with beta-galactosidase (lacZ). The International journal of developmental biology 15 10213086
1994 Expression of the Prevotella loescheii adhesin gene (plaA) is mediated by a programmed frameshifting hop. Journal of bacteriology 15 8144461
2021 Mice lacking PLAP-1/asporin counteracts high fat diet-induced metabolic disorder and alveolar bone loss by controlling adipose tissue expansion. Scientific reports 14 33654143
2019 1,25(OH)2D3 supports the osteogenic differentiation of hPDLSCs under inflammatory conditions through inhibiting PLAP-1 expression transcriptionally. International immunopharmacology 14 31837573
1996 Significance of placental alkaline phosphatase (PLAP) in the monitoring of patients with seminoma. British journal of urology 14 8653285
2022 Generation and Functional Characterization of PLAP CAR-T Cells against Cervical Cancer Cells. Biomolecules 13 36139135
2014 Overexpression of the PLAP-1 gene inhibits the differentiation of BMSCs into osteoblast-like cells. Journal of molecular histology 13 25038933
2007 Multiple functions of DOA1 in Candida albicans. Microbiology (Reading, England) 13 17379712
1999 The translational hop junction and the 5' transcriptional start site for the Prevotella loescheii adhesin encoded by plaA. Current microbiology 13 9841777
1994 Production of placental alkaline phosphatase (PLAP) and PLAP-like material by epithelial germ cell and non-germ cell tumours in vitro. British journal of cancer 13 8297725
2024 Isolation of serum-derived placental/amnio-chorionic extracellular vesicles across pregnancy by immunoaffinity using PLAP and HLA-G. Reproduction (Cambridge, England) 11 38428139
2014 Rapid 1α,25(OH)₂D ₃ membrane-mediated activation of Ca²⁺/calmodulin-dependent protein kinase II in growth plate chondrocytes requires Pdia3, PLAA and caveolae. Connective tissue research 11 25158196
2006 Placental alkaline phosphatase (PLAP) staining and human chorionic gonadotropin (hCG) production in cultures of fresh and cryopreserved cytotrophoblasts isolated by CD9/MHC class I/MHC class II immunoelimination. Placenta 11 16782189
2005 Placental alkaline phosphatase (PLAP) study in diabetic human placental villi infected with Trypanosoma cruzi. Placenta 11 15664416
1990 Serum placental alkaline phosphatase (PLAP) in gynecologic malignancies--with special reference to the combination of PLAP and CA54/61 assay. Clinica chimica acta; international journal of clinical chemistry 11 2178810
2017 Disulfide loop cleavage of Legionella pneumophila PlaA boosts lysophospholipase A activity. Scientific reports 10 29176577
2011 Computational modeling of the catalytic mechanism of human placental alkaline phosphatase (PLAP). Journal of chemical information and modeling 10 21939286
2005 Identification and molecular cloning of a gene encoding Phospholipase A2 (plaA) from Aspergillus nidulans. Biochimica et biophysica acta 10 16051517
2005 Placental alkaline phosphatase (PLAP) enzyme activity and binding to IgG in Chagas' disease. Placenta 10 16122790
2022 Distribution of Kazachstania Yeast in Thai Traditional Fermented Fish (Plaa-Som) in Northeastern Thailand. Journal of fungi (Basel, Switzerland) 9 36294595
1989 Rheumatoid arthritis synovial fluid phospholipase A2 activating protein (PLAP) stimulates human neutrophil degranulation and superoxide ion production. Agents and actions 9 2552770
2014 Catalytic activity of human placental alkaline phosphatase (PLAP): insights from a computational study. The journal of physical chemistry. B 8 25409280
2013 A novel cell-processing method 'AgarCytos' in conjunction with OCT3/4 and PLAP to detect intratubular germ cell neoplasia in non-obstructive azoospermia using remnants of testicular sperm extraction specimens. Human reproduction (Oxford, England) 8 23900208
2023 Degradation of α-Subunits, Doa1 and Doa4, are Critical for Growth, Development, Programmed Cell Death Events, Stress Responses, and Pathogenicity in the Watermelon Fusarium Wilt Fungus Fusarium oxysporum f. sp. niveum. Journal of agricultural and food chemistry 7 37486296
2015 Overexpression of PLAP-1 in bone marrow stromal cells inhibits the rat critical-size skull defect repair. Journal of molecular histology 7 26031659
2004 Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma. Gynecologic oncology 7 15491750
1996 A potential use of a monoclonal antibody to placental alkaline phosphatase (PLAP) to detect lymph node metastases of seminoma. The Journal of urology 7 7490882
1994 Activation of mechanonociceptors by pro-inflammatory peptides melittin and PLAP peptide. Experimental brain research 7 7813648
2010 Crystal structure of a PFU-PUL domain pair of Saccharomyces cerevisiae Doa1/Ufd3. The Kobe journal of medical sciences 6 21063153
2003 Double immunolabeling by the RBM and the PLAP markers for identifying intratubular (in situ) germ cell neoplasia of the testis. International journal of surgical pathology 6 12598912
2002 Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP). Human mutation 6 11857742
2020 Germ cells positive for PLAP and c-Kit in 11-16 year old normal boys with ongoing spermatogenesis. Pediatric surgery international 5 32772137
2016 Doa1 is a MAD adaptor for Cdc48. The Journal of cell biology 5 27044894
2023 Mice Lacking PLAP-1/Asporin Show Alteration of Periodontal Ligament Structures and Acceleration of Bone Loss in Periodontitis. International journal of molecular sciences 4 37958972
2023 Structure-function relationships underpin disulfide loop cleavage-dependent activation of Legionella pneumophila lysophospholipase A PlaA. Molecular microbiology 4 38130174
2011 Identification and molecular cloning Moplaa gene, a homologue of Homo sapiens PLAA, in Magnaporthe oryzae. Microbiological research 4 21482087
2025 SG-ML-PLAP: A structure-guided machine learning-based scoring function for protein-ligand binding affinity prediction. Protein science : a publication of the Protein Society 3 39660955
2025 Placental alkaline phosphatase (PLAP): Is it exclusively placental? Placenta 3 39793469
2022 Reciprocal role of PLAP-1 in HIF-1α-mediated responses to hypoxia. Journal of periodontal research 3 35138637
2010 Specificity and sensitivity of differentiation antigens in superficial soft tissue tumors: comparison of SMA, calponin, H-caldesmon, C-kit, PLAP and HPL. Bratislavske lekarske listy 3 21033622
2010 [Construction and confirmation of a recombinant eukaryotic expression plasmid pBABE-hygro-PLAP-1]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 3 21431266
2024 Allelic heterogeneity and abnormal vesicle recycling in PLAA-related neurodevelopmental disorders. Frontiers in molecular neuroscience 2 38650658
2020 Alkaline Phosphatases: in Silico Study on the Catalytic Effect of Conserved Active Site Residues Using Human Placental Alkaline Phosphatase (PLAP) As a Model Protein. Journal of chemical information and modeling 2 33306371
2014 Molecular determinants of the interaction between Doa1 and Hse1 involved in endosomal sorting. Biochemical and biophysical research communications 2 24607902
1996 [Determination of placental alkaline phosphatase (PLAP) for detecting the damages of alveolar type I cells caused by smoke inhalation]. Zhonghua zheng xing shao shang wai ke za zhi = Zhonghua zheng xing shao shang waikf [i.e. waike] zazhi = Chinese journal of plastic surgery and burns 2 9387432
2025 PLAA/UFD-3 regulates P-bodies through its intrinsic disordered domain. Proceedings of the National Academy of Sciences of the United States of America 1 40560612
2020 The phospholipase A effector PlaA from Legionella pneumophila: expression, purification and crystallization. Acta crystallographica. Section F, Structural biology communications 1 32133999
2001 Isolation of antibody to human placental alkaline phosphatase (PLAP) from extracts of human placentae. American journal of reproductive immunology (New York, N.Y. : 1989) 1 11506080
1995 Distribution of placental alkaline phosphatase gene (PLAP) frequencies in two groups of Muslim populations of Andhra Pradesh. Gene geography : a computerized bulletin on human gene frequencies 1 8845338
1987 Structural relationships between the isoenzymes of human placental alkaline phosphatase: a serum factor converts M-PLAP to A- and B-PLAP. Placenta 1 3658925
2026 PLAP Targeted Antibody-Radionuclide Conjugate for Theranostics in Pancreatic Cancer. Journal of medicinal chemistry 0 41989751
2024 PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder. International urology and nephrology 0 39680294
1996 Distribution of placental alkaline phosphatase (PLAP) gene frequencies in Andhra Pradesh (south India). Gene geography : a computerized bulletin on human gene frequencies 0 9049616