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prostaglandin D synthase 1; prostaglandin-H2 D-isomerase; glutathione-independent PGD synthetase; beta-trace protein; lipocalin-type PGD synthase; L-PGDS (PTGDS)
Function:
- one of 2 enzymes that catalyzes formation of PGD2 from PGH2
- lipocalin-type, glutathione independent
- binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid & thyroid hormone
- may act as a scavenger for harmful hydrophopic molecules
- secretory retinoid & thyroid hormone transporter (putative)
- role in development & maintenance of barriers (putative)
a) blood-brain barrier
b) blood-retina barrier
c) blood-aqueous humor barrier
d) blood-testis barrier
- roles in both maturation & maintenance of the central nervous system & male reproductive system (putative)
Structure:
- both N-glycosylation recognition sites are almost quantitatively occupied by N-glycans of the biantennary complex type, with a considerable proportion of structures bearing a bisecting GlcNAc
- agalacto structure as well as sialylated & nonsialylated oligosaccharides bearing alpha2-3- &/or alpha2-6-linked neuNAc are present
- belongs to the calycin superfamily, lipocalin family
Compartment:
- rough endoplasmic reticulum
- nuclear membrane
- Golgi
- cytoplasm
- perinuclear region
- secreted
- detected on rough endoplasmic reticulum of arachnoid & menigioma cells
- localized to the nuclear envelope, Golgi, secretory vesicles & spherical cytoplasmic structures in arachnoid trabecular cells, & to circular cytoplasmic structures in meningeal macrophages & perivascular microglial cells
- in oligodendrocytes, localized to rough endoplasmic reticulum & nuclear envelope
- in retinal pigment epithelial cells, localized to distinct cytoplasmic domains including perinuclear region
- also secreted
Expression:
- abundant in the brain & CNS
- expressed in tissues of the blood-brain barrier & secreted into cerebrospinal fluid
- abundantly expressed in heart
- in the male reproductive system, expressed in testis, epididymis & prostate, & is secreted into the seminal fluid
- expressed in the eye & secreted into the aqueous humor
- lower levels detected in various tissue fluids such as serum, normal urine, ascitic fluid & tear fluid
- also found in a number of other organs including ovary, fimbriae of the fallopian tubes, kidney, leukocytes
- expression in the amniotic fluid increases during weeks 12 to 25 of pregnancy; levels decrease slowly after 25 weeks
- induced by IL-1 beta & thyroid hormone
- probably induced by dexamethasone, dihydrotestosterone, progesterone, retinoic acid & retinal
- repressed by the notch-Hes signaling pathway
Pathology:
- urinary & serum levels of PTGDS may be an indicator of renal damage in diabetes mellitus & hypertension
- elevated levels in the coronary circulation may also be associated with angina pectoris
- changes in charge & molecular weight microheterogeneity, due to modification of the N-linked oligosaccharides, may be associated with neurodegenerative disease & multiple sclerosis
- detected in meningioma but not in other brain tumors; may be a specific cell marker for meningioma
- expression levels in amniotic fluid are altered in abnormal pregnancies; levels are lower in pregnancies with trisomic fetuses & fetuses with renal abnormalities
General
glycoprotein
isomerase
lipocalin
membrane protein
Properties
SIZE: MW = 21 kD
entity length = 190 aa
COMPARTMENT: cytoplasm
nuclear membrane
golgi
endoplasmic reticulum
MOTIF: signal sequence {1-22}
N-glycosylation site {N51}
cysteine residue {C65}
N-glycosylation site {N78}
cysteine residue {C89}
MODIFICATION: cysteine residue {C186}
cysteine residue {C186}
MODIFICATION: cysteine residue {C89}
Database Correlations
OMIM 176803
UniProt P41222
Pfam PF00061
Entrez Gene 5730
KEGG correlations
ENZYME 5.3.99.2
References
- UniProt :accession P41222
- SeattleSNPs
http://pga.gs.washington.edu/data/ptgds/