Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G protein-coupled receptors (GPCRs) are involved in cell recognition and signaling and their function has been experimentally determined by ligand activation and site-directed mutagenesis. Structurally, GPCRs consist of an extracellular N-terminus and an intracellular C-terminus separated by seven helical transmembrane domains (TM7). The extracellular region is highly glycosylated. The intracellular region binds to G proteins. An epididymal GPCR, designated HE6 (for human epididymis-specific protein 6), is present in the stereocilia projecting from the apical domain of principal cells into the epididymal lumen. In conceptual terms, HE6 wears two hats: an unusually long extracellular region characteristic of cell adhesion proteins, and an intracellular region with binding affinity to G protein. The binding partner to the long extracellular region has not been identified. HE6 has another remarkable feature comparable to the GPCR calcium-independent receptor of alpha-latrotoxin, designated CIRL. Both HE6 and CIRL are endogenously cleaved into two pieces at the GPCR proteolytic site (GPS) located adjacent to TM1, the first of the seven transmembrane helices. One fragment of the heterodimer wears the cell adhesion hat; the other retains the typical characteristics of GPCRs. This proteolytic processing may be regarded as a mechanism of molecular compartmentalization of cell adhesion and G protein activation functions. The latter may engage a beta-arrestin-driven endocytic trafficking mechanism independent from the adhesive properties of the mucin extracellular domain. It is also conceivable that events taking place in the epididymal lumen can be surveyed by the long adhesive rod and subsequently coupled inside principal cells to a signaling cascade.
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PMID:Epididymal G protein-coupled receptor (GPCR): two hats and a two-piece suit tailored at the GPS motif. 1242 Feb 93

Human Epididymis-specific protein 6 [HE6 (GPR64)] is a highly conserved, tissue-specific seven-transmembrane receptor of the human epididymis. The rodent counterparts were cloned and 5'-inverse PCR employed to confirm that the cDNA sequences were full length. Downstream from the highly conserved signal peptide-coding sequence, the 5'-regions contained at least six mini-exons of less than 50 nucleotides. Multiple splice variants involving these mini-exons were cloned in the human, the majority of which was also found in rodents. Northern blot analysis showed that the tissue distribution of the mRNA was very similar in human and rodents. The human HE6 gene was assigned to the X chromosome in a region, which is syntenic to the mouse. The HE6 sequence predicted a two-subunit receptor of the LNB-TM7 subfamily. A membrane preparation and protein solubilization method was adopted to identify the endogenous epididymal proteins. Two sets of peptides were chosen for antibody production, assuming that protein scission had occurred within the conserved GPS-motif. Western blot analysis revealed abundant two-subunit proteins in human and rodents, comprising an approximately 180 kDa hydrophilic ectosubunit and a <40 kDa hydrophobic endosubunit. Deglycosylation experiments showed that the large ectosubunits were highly glycosylated, the carbohydrate side chains dramatically increasing the apparent molecular mass. Immunohistochemical studies revealed that both subunits were associated with apical membranes of efferent ductule and proximal epididymal duct epithelia.
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PMID:HE6, a two-subunit heptahelical receptor associated with apical membranes of efferent and epididymal duct epithelia. 1242 Feb 95