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

The epididymal epithelial cells of the lizard (Lacerta vivipara) produce large amounts of specific proteins under androgenic control. Amongst them, a major protein family that binds to the head of spermatozoa, the lizard epididymal secretory protein (LESP) family, has been identified as a member of the lipocalin superfamily. LESPs are composed of 9 elements that present an identical molecular mass of 18 000 Da but have a large range of pHi (3.5 to 9). The structural analysis of this protein family was performed by the determination and comparison of both the aminoterminal sequence of each element and the complete sequence of three specific LESP cDNA clones. When not identical, LESP elements present randomly dispatched nucleotide and amino acid substitutions, indicating the existence of at least five LESP mRNA populations encoded by a multigenic family. We determined that these LESP genes are differentially expressed during the annual epididymal cycle.
 ...
PMID:The lipocalin sperm coating lizard epididymal secretory protein family: mRNA structural analysis and sequential expression during the annual cycle of the lizard, Lacerta vivipara. 1065 4

A major epididymal secretory protein in men has a colinear cDNA sequence with lymphocyte CD52, a sialylated glycoprotein. Immunostaining and flow cytometric detection of cynomolgus monkey sperm CD52 during epididymal maturation showed increases from 20 to 85% stained sperm from the caput to the corpus with staining intensities doubled. Freshly prepared cauda sperm showed only 10% staining while they markedly increased in percentage and intensity of staining upon incubation at 37 degrees C under capacitating conditions, but not at 4 degrees C. Western blotting of proteins from fresh cauda sperm revealed no less antigen than corpus sperm. Staining of ejaculated sperm exhibited similar increases during incubation. Further washing with a high salt medium before staining to remove any electrostatically-bound molecules masking the antigen showed no effect. Incubation-induced increases in antigen binding were accelerated by the addition of neuraminidase (0.25 and 0.5 U/ml), but not affected by the sialyl residue-rich fetuin (5 mg/ml) competing for any endogenous neuraminidase. There were no concomitant decreases in the staining of sialic acid residues during capacitation-incubation. These findings suggest a cryptic antigen epitope site as a consequence of sperm maturation and subsequent re-exposure under capacitation conditions, but not due to the removal of sialic acid residues by endogenous neuraminidase. Involvement of endogenous proteases was also ruled out, as incubation in the presence of protease inhibitors did not hinder the increases but resulted in a dose-dependent enhancement in staining, suggesting some protease-sensitive unmasking process. In conclusion, the monkey epididymal secreted CD52 on sperm underwent changes in antigenic characteristics during sperm maturation which were reversed under capacitation conditions.
 ...
PMID:Maturational changes of the CD52-like epididymal glycoprotein on cynomolgus monkey sperm and their apparent reversal in capacitation conditions. 1101 36

Even though the epididymis produces an environment promoting sperm maturation and viability, some sperm do not survive transit through the epididymal tubule. Mechanisms that segregate the epididymal epithelium and/or the viable sperm population from degenerating spermatozoa are poorly understood. We report here the identification and characterization of HEP64, a 64-kDa glycoprotein secreted by principal cells of the corpus and proximal cauda epididymidis of the hamster that specifically binds to and coats dead/dying spermatozoa. The HEP64 monomer contains approximately 12 kDa carbohydrate and, following chemical deglycosylation, migrates as a approximately 52-kDa polypeptide. Both soluble (luminal fluid) and sperm-associated HEP64 are assembled into disulfide-linked high molecular weight oligomers that migrate as a doublet band of 260/280 kDa by nonreducing SDS-PAGE. In the epididymal lumen, HEP64 is concentrated into focal accumulations containing aggregates of structurally abnormal or degenerating spermatozoa, and examination of sperm suspensions reveals that HEP64 forms a shroudlike coating surrounding abnormal spermatozoa. The HEP64 glycoprotein firmly binds degenerating spermatozoa and is not released by either nonionic detergent or high salt extraction. Electron microscopic immunocytochemistry demonstrates that HEP64 localized to an amorphous coating surrounding the abnormal spermatozoa. The potential mechanisms by which this epididymal secretory protein binds dead spermatozoa as well as its possible functions in the sperm storage function of the cauda epididymidis are discussed.
 ...
PMID:Identification of a hamster epididymal region-specific secretory glycoprotein that binds nonviable spermatozoa. 1105 48

Prostaglandin D2 synthase (PGDS) is a major epididymal secretory protein in several species. We quantified PGDS in ram and bull semen using a specific antiserum. Strong variations in PGDS concentration existed between animals. In the bull, the highest concentrations were found preferentially in animals with normal or high fertility, as was previously suggested. However, low concentrations were found in males with all ranges of fertility, suggesting that the function of PGDS either is not necessary for male fertility or can be assumed by other proteins when its concentration is low. In the ram and stallion, cDNA and deduced protein sequences of PGDS were obtained by reverse transcription-polymerase chain reaction and showed that PGDS possessed the sequences involved in the three-dimensional folding characteristic of the lipocalin family and a cysteine at position 65 that is involved in the enzymatic activity. The enzymatic activity of PGDS was estimated in the ram by in vitro incubation of epididymal-isolated tubules with radioactive arachidonic acid. Prostaglandin (PG) D2 represented approximately 10% of the PGs produced in the lumen, irrespective of the presence or absence of luminal PGDS, suggesting that this protein is not involved in PGD2 biosynthesis. These results were corroborated by the absence of conversion of PGH2 to PGD2 when epididymal fluids were incubated with PGH2. In the rat, inhibition of PG biosynthesis in vivo by nonsteroidal anti-inflammatory drugs for 60 days did not change spermatozoa mobility or male fertility. It is likely that PGDS, which has a structure similar to that of lipocalin, functions as a lipophilic carrier protein, because we have shown that epididymal PGDS binds retinoic acid and testosterone in vitro.
 ...
PMID:Mammalian lipocalin-type prostaglandin D2 synthase in the fluids of the male genital tract: putative biochemical and physiological functions. 1180 63

Polyclonal antibody was used to partially characterize REP38, a major rabbit epididymal secretory protein. Western blot analyses and immunohistochemistry indicated that REP38 is only expressed in regions 5 and 6 of the epididymis (corpus epididy-midis) and is localized in the supranuclear region and microvilli of the principal cells in these regions. It was not expressed in other tissues of the body. In region 8 (cauda epididymidis), REP38 was detected in the luminal border and cytoplasm of scattered principal cells, indicating that it may be reabsorbed in this region. This protein accumulated on the sperm plasma membrane downstream of region 5 and was localized predominantly over the acrosomal and postacrosomal regions of the head and the middle piece. Although tightly bound to epididymal sperm, REP38 migrated to the equatorial segment under conditions in vivo that would promote capacitation. When tested in vitro, anti-REP38 IgG reduced the percentage of ova fertilized in a concentration-dependent manner, apparently by blocking sperm-egg fusion.
 ...
PMID:Rabbit epididymal secretory proteins. II. Immunolocalization and sperm association of REP38. 1208 10

REP38 is a rabbit epididymal secretory protein of 38 kDa that has recently been shown to interact with spermatozoa. A rabbit epididymal cDNA expression library was screened with a polyclonal antibody raised against REP38. A single clone (REP38-c1) with an open reading frame encoding a polypeptide of 666 amino acids was obtained. Cleavage of a 22-amino acid N-terminal signal peptide revealed a mature protein with a theoretical molecular mass of 74.5 kDa. Northern blot analysis revealed the presence of two cross-hybridizing transcripts of approximately 1.3 and 2.5 kilobases that appear to result from alternative mRNA splicing. This finding may explain the discrepancies between the observed (38 kDa) and deduced molecular mass of REP38. Expression of both transcripts was epididymis specific and was detected only in regions 2-6. During development, the expression of REP38-c1 mRNA was initiated between 1 and 2 mo postnatum and therefore precedes the appearance of sperm within the lumen of the epididymis. These findings are in agreement with the immunohistochemical localization of the REP38 protein. Androgen deprivation induced by orchidectomy reduced REP38-c1 mRNA levels below the limit of detection, an effect that was reversed by administration of exogenous testosterone. Although REP38-c1 mRNA was detected only in the rabbit epididymis, database searches indicated homology with two rat testis specific cDNAs, KTT4 and odf2, which encode sperm outer dense fiber proteins.
 ...
PMID:Rabbit epididymal secretory proteins. III. Molecular cloning and characterization of the complementary DNA for REP38. 1208 11

Complement C4b-binding protein (C4BP) is a plasma protein synthesized in the liver and plays a regulatory role in the host defense complement system. We have previously reported that mRNAs of the C4BP alpha chain (C4BPalpha) are expressed at significant levels in the guinea pig and mouse epididymis in an androgen-dependent manner. Here, we analyze the murine C4bpa gene and show that epididymal and liver C4BPalpha mRNAs are generated from a single-copy gene and that the epididymal C4BPalpha mRNAs are transcribed from novel transcription start sites located approximately 100 base pairs downstream from those used in the liver. Furthermore, in an immunohistochemical study using rabbit anti-mouse C4BP antiserum, we demonstrated that C4BP is localized in the stereocilia and Golgi apparatus of the epididymal epithelial cells and the surfaces of spermatozoa in the lumen in the region from the distal caput to the cauda but not in the proximal caput region. Indirect immunofluorescence of the isolated spermatozoa demonstrated that C4BP is localized preferentially on the head region of the spermatozoa, and immunoelectron microscopy located C4BP on the plasma membrane and the outer acrosomal membrane. These results indicate that epididymal C4BP is synthesized in the epithelial cells and secreted into the lumen in a region-restricted manner and is taken up to the sperm membranes on passage through the epididymis. Many epididymal proteins are secreted from the epithelial cells in a region-specific and androgen-dependent manner and are considered to contribute to sperm maturation. Our findings suggest a novel function of C4BP as one such epididymal secretory protein.
 ...
PMID:Complement C4b-binding protein as a novel murine epididymal secretory protein. 1293 Jul 19

As part of a systematic study of rabbit epididymal proteins involved in sperm maturation, we have identified and characterized a novel glycoprotein (rabbit epididymal secretory protein 52 [REP52]) of 52 kDa. REP52 is synthesized and secreted in a tissue-specific manner by the mid (region 6) and distal (region 7) corpus epididymidis and associates weakly with the sperm surface overlying the principal piece of the tail. Sequencing of cloned REP52 cDNA demonstrated that this protein represents a novel member of the highly conserved fibronectin type II (FN2) module protein family. The protein appears related but not homologous to ungulate seminal plasma proteins and is the first known example to be identified as a rabbit epididymal secretory protein. Consistent with other members of this protein family, REP52 possessed a high level of sequence identity within the FN2 module-encoding domains, but a highly variable N-terminal sequence that failed to show significant homology with published sequences. By analogy with evidence from studies of the ungulate seminal plasma proteins it is hypothesized that the tandemly arranged FN2 modules could facilitate the association of REP52 with sperm phosphatidylcholine residues on the outer leaflet of the sperm tail. It is also considered likely that these domains represent key elements for the function of this novel protein, a conclusion supported by the fact that antisera raised against the REP52 protein blocked in vitro fertilization in a concentration-dependent fashion.
 ...
PMID:Molecular and functional characterization of the rabbit epididymal secretory protein 52, REP52. 1819 86


<< Previous 1 2