Platelet-activating factor acetylhydrolase IB subunit alpha1 (PAFAH1B3)
The protein contains 231 amino acids for an estimated molecular weight of 25734 Da.
Alpha1 catalytic subunit of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) heterotetrameric enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and modulates the action of PAF. The activity and substrate specificity of PAF-AH (I) are affected by its subunit composition. Both alpha1/alpha1 homodimer (PAFAH1B3/PAFAH1B3 homodimer) and alpha1/alpha2 heterodimer(PAFAH1B3/PAFAH1B2 heterodimer) hydrolyze 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid (AAGPA) more efficiently than PAF, but they have little hydrolytic activity towards 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE). Plays an important role during the development of brain. (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs1043818 |
Biological Process
Brain development
Lipid catabolic process
Lipid metabolic process
Nervous system development
Spermatogenesis
The reference OMIM entry for this protein is 603074
Platelet-activating factor acetylhydrolase, isoform 1b, gamma subunit; pafah1b3
DESCRIPTION
Platelet-activating factor acetylhydrolase (PAFAH) catalyzes the removal of the acetyl group at the sn-2 position of the glycerol backbone of platelet-activating factor (PAF), producing biologically inactive lyso-PAF. Isoform 1B of PAFAH consists of 3 subunits: alpha (PAFAH1B1; 601545), beta (PAFAH1B2; 602508), and gamma. The catalytic activity of the enzyme resides in the beta and gamma subunits, whereas the alpha subunit has regulatory activity (summary by Adachi et al., 1995).CLONING
By screening a human fetal liver cDNA library with oligonucleotides based on the cDNA sequence of the bovine PAFAH-gamma subunit, Adachi et al. (1995) cloned a cDNA encoding PAFAH1B3. The deduced 231-amino acid human protein has 97.8% identity with the bovine PAFAH-gamma subunit. Southern blot analysis showed that PAFAH1B3 is a single-copy gene in the human genome. Northern blot analysis detected a 1.0-kb PAFAH1B3 transcript in several human adult and fetal tissues, with the highest expression in fetal brain. Adachi et al. (1995) expressed the PAFAH1B3 cDNA in E. coli and found that the resulting protein was catalytically active, demonstrating that trimer formation is not essential for PAFAH1B3 activity.GENE STRUCTURE
Adachi et al. (1995) determined that the PAFAH1B3 gene spans approximately 5.6 kb and contains 5 exons.MAPPING
By radiation hybrid mapping and fluorescence in situ hybridization, Moro et al. (1998) localized the PAFAH1B3 gene to chromosome 19q13.1.GENE FUNCTION
Zhou et al. (2011) determined that aspirin (acetylsalicylic acid) is hydrolyzed and rendered biologically inactive by type I platelet-activating factor, and that the reaction occurs intracellularly within erythrocytes. Hydrolase activity could be mediated by either of the 2 catalytic subunits, PAFAH1B2 (602508) or PAFAH1B3, but not by plasma PAF (PLA2G7; 601690). In vitro studies showed that exposing platelets to aspirin and erythrocytes decreased the ability of aspirin to inhibit thromboxane A2 synthesis and platelet aggregation, and aspirin preincubated with erythrocytes was almost completely ineffective as a platelet inhibitor. Analysis of 10 different healthy blood donors revealed that aspirin hydrolysis varied more than 2-fold, and this variation corresponded to the erythrocyte protein content of PAFAH1B2, as determined by immunoblot, but did not correspond to levels of PAFAH1B3. Zhou et al. (2011) concluded that intracellular type I PAF acetylhydrolase is the major aspirin hydrolase in human blood (erythrocytes), and that variation in this hydrolase activity may underlie the variation in therapeutic response among humans. Using whole-genome sequencing to identify genes involved in high-altitude adaptation in 2 ethnically distinct groups of Ethiopian highlanders living at 3,500 meters above sea level on Bale Plateau or Chennek field in Ethiopia, Udpa et al. (2014) identified regions with significant loss of diversity, including a region on chromosome 19 that contains 8 genes, including CIC (612082), LIPE (151750), and PAFAH1B3. The authors evaluated the roles of these genes in hypoxia tolerance by using small interfering RNA in Drosophila. Knockdown of Cic, Hsl, or Pafaha, the fly orthologs of CIC, LIPE, and PAFAH1B3, respectively, resulted in increased tolerance and survival in hypoxic environments. Udpa et al (2014) concluded that these genes may encode evolutionarily conserved proteins involved in hypoxia ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603074 was added.