Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2)

The protein contains 229 amino acids for an estimated molecular weight of 25569 Da.

 

Alpha2 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. The alpha2/alpha2 homodimer (PAFAH1B2/PAFAH1B2 homodimer) hydrolyzes PAF and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE) more efficiently than 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid (AAGPA). In contrast, the alpha1/alpha2 heterodimer(PAFAH1B3/PAFAH1B3 heterodimer) hydrolyzes AAGPA more efficiently than PAF, but has little hydrolytic activity towards AAGPE (By similarity). May play a role in male germ cell meiosis during the late pachytenestage and meiotic divisions as well as early spermiogenesis (By similarity). (updated: Feb. 10, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 100

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The reference OMIM entry for this protein is 602508

Platelet-activating factor acetylhydrolase, isoform 1b, beta subunit; pafah1b2

DESCRIPTION

Platelet-activating factor (PAF) is a biologically active phospholipid with diverse biologic effects. PAF is degraded to inactive products by hydrolysis of the acetyl group at the sn-2 position to produce the biologically inactive products LYSO-PAF and acetate. This reaction is catalyzed by PAF acetylhydrolase (PAFAH). The various monomeric and multimeric forms of the enzyme are composed of alpha (601545), beta, and gamma (603074) PAFAH subunits.

CLONING

By screening a human fetal liver library with 2 oligodeoxyribonucleotides derived from the cDNA sequence of the bovine PAFAH beta subunit, Adachi et al. (1997) cloned the cDNA encoding the human PAFAH beta subunit. The PAFAH1B2 gene encodes a 229-amino acid polypeptide with a molecular mass of 30 kD. The human PAFAH1B2 amino acid sequence is 62.4% identical to that of the human gamma subunit. Northern blot analysis revealed that the gene was expressed as a 4.0-kb mRNA in all human adult and fetal tissues tested.

MAPPING

By radiation hybrid mapping, screening of a YAC library, and fluorescence in situ hybridization, Moro et al. (1998) localized the PAFAH1B2 gene to 11q23.

GENE FUNCTION

By analysis of crystalline structures of mouse proteins, Tarricone et al. (2004) determined that a Lis1 (601545) homodimer binds with a homodimer of either Pafah1b2 or Ndel1 (607538) to form a tetramer. Ndel1 competes with the Pafah1b2 homodimer for Lis1, but the interaction is complex and requires both the N- and C-terminal domains of Lis1. The data suggested that the Lis1 molecule undergoes major conformational changes when switching from a complex with the acetylhydrolase to that with Ndel1. By studying human erythrocytes, Zhou et al. (2011) determined that aspirin (acetylsalicylic acid) is hydrolyzed and rendered biologically inactive by type I PAF, and that the reaction occurs intracellularly within erythrocytes. Overexpression of the catalytic PAFAH1B2 or PAFAH1B3 (603074) subunits in HEK293 cells showed that each could hydrolyze aspirin. Inhibition of recombinant PAFAH1B2 reduced aspirin hydrolysis. In contrast, plasma PAF (PLA2G7; 601690) was devoid of aspirin hydrolase activity. 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 (see 608233). ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

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

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602508 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed