PLAA Gene - Phospholipase A2 Activating Protein
Comprehensive genomic and functional analysis of PLAA, a key regulator of ubiquitin signaling and neurodevelopment.
Gene Information Card
| Symbol | PLAA |
|---|---|
| Full Name | Phospholipase A2 Activating Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 9p21.2 |
| NCBI Gene ID | 5373 ncbi.nlm.nih.gov/gene/5373 |
| Ensembl ID | ENSG00000136826 |
| UniProt ID | Q9Y263 |
| OMIM ID | 603873 |
| HGNC ID | 9045 |
| Aliases | PLA2P, PLAP, PTPLA2 |
Description
PLAA (phospholipase A2 activating protein) encodes a protein that binds ubiquitin and regulates the ubiquitin-proteasome system. It is involved in endoplasmic reticulum-associated degradation (ERAD) and plays a critical role in synaptic development and maintenance. Mutations in PLAA are associated with neurodevelopmental disorders, including developmental and epileptic encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and epileptic encephalopathy 50 (DEE50) | Loss-of-function mutations impair ubiquitin-mediated protein degradation, leading to synaptic dysfunction and neuronal hyperexcitability. | ClinVar, OMIM |
| Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies | Disrupted PLAA function alters ERAD and ubiquitin signaling, affecting cortical development. | OMIM, PubMed |
| Intellectual disability | Missense variants reduce PLAA stability and ubiquitin binding, impairing synaptic plasticity. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.5 | High |
| Testis | 12.3 | Medium |
| Lung | 8.7 | Medium |
| Liver | 6.2 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model, high expression |
| HEK293 (embryonic kidney) | 10.8 | Common overexpression system |
| HeLa (cervical carcinoma) | 9.4 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.875G>A (p.Arg292His) | Missense | Rare | Reduced ubiquitin binding, loss of function |
| c.1132C>T (p.Arg378*) | Nonsense | Very rare | Premature truncation, loss of function |
| c.1543_1544del (p.Leu515Valfs*2) | Frameshift | Rare | Loss of function, associated with DEE50 |
Mutation functional classification
Loss of Function (LOF)
Most PLAA mutations are loss-of-function, leading to impaired ERAD and ubiquitin signaling, causing neurodevelopmental phenotypes.
Gain of Function (GOF)
No gain-of-function mutations reported in PLAA.
Dominant Negative (DN)
Not established; PLAA mutations are typically recessive or de novo dominant with haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • ubiquitin binding (GO:0043130) |
| • ubiquitin-dependent protein catabolic process (GO:0006511) | • ER-associated ubiquitin-dependent protein catabolic process (GO:0030433) |
| • cytoplasm (GO:0005737) | • nucleus (GO:0005634) |
Pathways
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• Endoplasmic reticulum-associated degradation (ERAD) (Reactome: R-HSA-983168)
Protein Summary
The PLAA protein (UniProt Q9Y263) is a 738-amino-acid ubiquitin-binding protein that contains a PFU (PLAA family ubiquitin-binding) domain. It acts as an adaptor in the ERAD pathway, facilitating the extraction of misfolded proteins from the endoplasmic reticulum for proteasomal degradation. PLAA is highly expressed in the brain and is essential for neuronal survival and synaptic function. Structural studies show that the PFU domain forms a ubiquitin-binding pocket critical for its cellular activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLAAT3 Knockout HEK293 Cell Line | EDJ-KQ1272 | Human | 11145 | Details Get a Quote |
| PLAAT4 Knockout HEK293 Cell Line | EDJ-KQ2046 | Human | 5920 | Details Get a Quote |
| PLAA Knockout HEK293 Cell Line | EDJ-KQ3176 | Human | 9373 | Details Get a Quote |
| PLAAT5 Knockout HEK293 Cell Line | EDJ-KQ7602 | Human | 117245 | Details Get a Quote |
| PLAAT1 Knockout HEK293 Cell Line | EDJ-KQ14779 | Human | 57110 | Details Get a Quote |
| PLAAT2 Knockout HEK293 Cell Line | EDJ-KQ14780 | Human | 54979 | Details Get a Quote |
| PLAAT4 Knockout A-549 Cell Line | EDJ-KQ22099 | Human | 5920 | Details Get a Quote |
| PLAAT4 Knockout HeLa Cell Line | EDJ-KQ22100 | Human | 5920 | Details Get a Quote |
| PLAAT3 Knockout A-549 Cell Line | EDJ-KQ20650 | Human | 11145 | Details Get a Quote |
| PLAAT3 Knockout HCT 116 Cell Line | EDJ-KQ20651 | Human | 11145 | Details Get a Quote |
| PLAAT3 Knockout HeLa Cell Line | EDJ-KQ20652 | Human | 11145 | Details Get a Quote |
| PLAA Knockout A-549 Cell Line | EDJ-KQ24600 | Human | 9373 | Details Get a Quote |
| PLAA Knockout HCT 116 Cell Line | EDJ-KQ24601 | Human | 9373 | Details Get a Quote |
| PLAA Knockout HeLa Cell Line | EDJ-KQ24602 | Human | 9373 | Details Get a Quote |
| PLAAT2 Knockout HeLa Cell Line | EDJ-KQ56515 | Human | 54979 | Details Get a Quote |
