SLCO2A1
Developmental stage
Expression in the uterus changes during the menstrual cycle (PubMed:15657371, PubMed:16339169). In endometrium, expression is higher in the menstrual, proliferative, and early secretory phases than in the mid-late secretory phase (PubMed:15657371, PubMed:16339169). In the ovaries, expression is ovulation-dependent, levels are negligible in preovulatory follicles, and increase in postovulatory follicles and in the corpus luteum (PubMed:27169804).
Function
Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane (PubMed:11997326, PubMed:26692285, PubMed:8787677). PGs and thromboxanes play fundamental roles in diverse functions such as intraocular pressure, gastric acid secretion, renal salt and water transport, vascular tone, and fever (PubMed:15044627). Plays a role in the clearance of PGs from the circulation through cellular uptake, which allows cytoplasmic oxidation and PG signal termination (PubMed:8787677). PG uptake is dependent upon membrane potential and involves exchange of a monovalent anionic substrate (PGs exist physiologically as an anionic monovalent form) with a stoichiometry of 1:1 for divalent anions or of 1:2 for monovalent anions (PubMed:29204966). Uses lactate, generated by glycolysis, as a counter-substrate to mediate PGE2 influx and efflux (PubMed:11997326). Under nonglycolytic conditions, metabolites other than lactate might serve as counter-substrates (PubMed:11997326). Although the mechanism is not clear, this transporter can function in bidirectional mode (PubMed:29204966). When apically expressed in epithelial cells, it facilitates transcellular transport (also called vectorial release), extracting PG from the apical medium and facilitating transport across the cell toward the basolateral side, whereupon the PG exits the cell by simple diffusion (By similarity). In the renal collecting duct, regulates renal Na+ balance by removing PGE2 from apical medium (PGE2 EP4 receptor is likely localized to the luminal/apical membrane and stimulates Na+ resorption) and transporting it toward the basolateral membrane (where PGE2 EP1 and EP3 receptors inhibit Na+ resorption) (By similarity). Plays a role in endometrium during decidualization, increasing uptake of PGs by decidual cells (PubMed:16339169). Involved in critical events for ovulation (PubMed:27169804). Regulates extracellular PGE2 concentration for follicular development in the ovaries (By similarity). Expressed intracellularly, may contribute to vesicular uptake of newly synthesized intracellular PGs, thereby facilitating exocytotic secretion of PGs without being metabolized (By similarity). Essential core component of the major type of large-conductance anion channel, Maxi-Cl, which plays essential roles in inorganic anion transport, cell volume regulation and release of ATP and glutamate not only in physiological processes but also in pathological processes (By similarity). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable).
Involvement in disease
PHOAR2-enteropathy syndrome
PHOAR2E
An autosomal recessive disease characterized by primary hypertrophic osteoarthropathy and/or chronic non-specific ulcers of the small intestine. Affected individuals present with digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Chronic ulcers of the small intestine result in abdominal pain and watery diarrhea, and are associated with chronic anemia. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.
None
The disease is caused by variants affecting the gene represented in this entry.
Hypertrophic osteoarthropathy, primary, autosomal dominant
PHOAD
A form of primary hypertrophic osteoarthropathy, a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. PHOAD patients may also experience joint swelling and pain, and some have reported gastrointestinal symptoms, including watery diarrhea. Males are more commonly affected, and more severely affected, than females.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the organo anion transporter (TC 2.A.60) family.
Tissue Specificity
Ubiquitous (PubMed:22331663, PubMed:8787677). Significant expression observed in lung, kidney, spleen, and heart (PubMed:22331663). Expressed in the endometrium (at both mRNA and protein levels) (PubMed:15657371, PubMed:16339169). Expressed in the ovaries (at mRNA and protein levels) (PubMed:27169804). In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed within the tubules (PubMed:35307651).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Basal cell membrane
- Multi-pass membrane protein
- Cytoplasm
- Lysosome
- Localized to the basal membrane of Sertoli cells.
Alternative names
OATP2A1, SLC21A2, SLCO2A1, Solute carrier organic anion transporter family member 2A1, PHOAR2, Prostaglandin transporter, Solute carrier family 21 member 2, PGT