Prostaglandin E synthase 3 (PTGES3)

The protein contains 160 amino acids for an estimated molecular weight of 18697 Da.

 

Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes (PubMed:11274138, PubMed:12077419). Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway (PubMed:24711448). (updated: April 1, 2015)

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.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 78%
Model score: 27
MODL_MODELLER-9.18

(right-click above to access to more options from the contextual menu)

The reference OMIM entry for this protein is 607061

Prostaglandin e synthase 3; ptges3
Unactive progesterone receptor, 23-kd; p23
Prostaglandin e synthase, cytosolic; cpges

CLONING

P23 was first observed as a component of the unactivated avian progesterone receptor complex, along with HSP70 (see 140550) and HSP90 (see 140571) (Smith et al., 1990). Using the chicken p23 sequence as probe, Johnson et al. (1994) cloned P23 from a human testis cDNA library. The deduced 160-amino acid protein has a calculated molecular mass of about 19 kD and contains several putative phosphorylation sites. P23 shares about 96% sequence identity with the chicken homolog. Western blot analysis revealed a 23-kD band in tissue and cell lysates from several mammalian species including human.

GENE FUNCTION

Freeman and Yamamoto (2002) determined that the P23 molecular chaperone localizes to genomic response elements in a hormone-dependent manner and showed that it could disrupt receptor-mediated transcriptional activation. Synthesis of prostaglandin E2 (PGE2) from arachidonic acid involves multiple enzymes, and 2 isoforms of the terminal enzyme of this biosynthetic pathway, PGE synthase (PGES), have been identified. Cytosolic PTGES (cPGES) is identical to the heat-shock protein-90 (see 140571) chaperone p23 (Tanioka et al., 2000) and is functionally coupled to constitutive prostaglandin-endoperoxide H synthase-1 (176805) (Han et al., 2002). Microsomal PTGES (mPGES; 605172) is inducible by proinflammatory cytokines such as IL1B (147720). Meadows et al. (2003) studied expression and localization of both enzyme isoforms in human fetal membranes either at term or preterm, with or without labor. Western blot analysis of the amnion and choriodecidua showed no differences in amounts of either cPGES or mPGES at term or preterm, with or without labor, in either tissue with advancing gestation. Meadows et al. (2003) concluded that expression of PGES is not the rate-limiting step in PGE2 synthesis in fetal membranes at labor.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the P23 gene to chromosome 12 (TMAP SHGC-35709). ... More on the omim web site

Subscribe to this protein entry history

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 607061 was added.