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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel human cDNA encoding a small secretory glycopeptide specifically expressed within the caput and proximal corpus regions of the human epididymis, HE2, has been cloned and sequenced. Southern hybridization analysis showed it to be derived from a single-copy gene. A subclone containing the coding region of the mature peptide was used to generate the putatively encoded peptide as a 10,000 M(r) recombinant fusion protein in a bacterial expression system. This recombinant HE2 protein, as well as an oligopeptide deduced from the open-reading frame, was used to raise polyclonal antisera. Immunohistochemistry and immunofluorescence showed that the predicted HE2 peptide is present in the epididymal epithelium and on the sperm surface, where it adopts a typical antigenic pattern with a subacrosomal equatorial distribution on the sperm head.
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PMID:Molecular cloning and characterization of a novel human sperm antigen (HE2) specifically expressed in the proximal epididymis. 816 23

Three tissue-specific gene probes that had been isolated by differential screening from a human epididymal cDNA library--HE1, HE2, and HE5--were employed to investigate regional specializations in the human epididymis. All 3 cDNAs were derived from major transcripts of the epithelial cells lining the epididymal duct. Each mRNA species, however, exhibited a discrete longitudinal pattern of hybridization with maxima in different regions of this organ, suggesting regional specializations of gene expression. The HE5 mRNA, which was recently shown to encode the peptide backbone of the human leukocyte differentiation antigen CDw52, showed maximum levels in the distal corpus epididymidis and in the vas deferens, whereas the HE2 mRNA was found predominantly in the caput and proximal corpus sections of the epididymis. HE1 mRNA was found in high amounts in all parts of the epididymis, displaying a 2-peak expression pattern with maxima in the distal caput and distal corpus of the epididymal duct.
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PMID:Region-specific variation of gene expression in the human epididymis as revealed by in situ hybridization with tissue-specific cDNAs. 841 12

By using various methods, ranging from conventional protein separation and purification to monoclonal antibody and cDNA cloning strategies, a considerable body of information has been obtained on mammalian epididymal proteins. Molecular characterization of proteins specifically produced in the human epididymis has been achieved by cDNA cloning, followed by raising antibodies against synthetic peptide epitopes. The predicted proteins have been localized in the human epididymal epithelium, within the lumen of the epididymal duct and vas deferens, and also on the surface of ejaculated spermatozoa. Sperm association has been reported for at least four human epididymal proteins, ARP, HE2, HE4, and HE5/CD52. However, as is largely the case in other species, a link to a specific function for any luminal component of the human epididymis, including the cloned secretory glycoproteins, to either sperm maturation or storage has not yet been demonstrated convincingly. Indirect evidence for a function for epididymal proteins comes from their relatively high frequency and tissue-specific expression as well as from their distinct spatial expression patterns along the human epididymal duct. However, it remains to be established (for example, by using the proteins and their antibodies in functional tests) whether, besides being essential markers of sperm maturation, they are also functionally important.
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PMID:Molecular characterization of epididymal proteins. 968 87

A cDNA clone of chimpanzee EP2 was obtained from epididymal RNA by RT-PCR and was sequenced. Chimpanzee EP2 and human HE2 cDNA were > 99% identical and the proteins were 100% identical. The derived amino acid sequence of chimpanzee EP2 showed a consensus sequence for a leader peptide typical of secreted proteins. Northern blot analysis indicated that expression of the gene encoding chimpanzee EP2 is specific to the epididymis and not to other chimpanzee tissues examined. RT-PCR and northern blot analysis of epididymides recovered from an androgen deprived adult male chimpanzee showed that the expression of EP2 is androgen dependent.
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PMID:HE2/EP2, an androgen-dependent protein from the epididymis of the chimpanzee, Pan troglodytes. 1064 80

The EP2 gene codes for a family of androgen-dependent, epididymis-specific secretory proteins. Using probes derived from human HE2 cDNA, a chimpanzee epididymal cDNA library was screened. Five variants of chimpanzee EP2 cDNA were identified. Variant 1 (EP2A) is the chimpanzee ortholog of HE2. Variant 2 (EP2B) has an alternative 5' end. Variant 3 (EP2C) has an alternative 3' end. Two additional variants were identified by reverse transcriptase-polymerase chain reaction analysis. Variant 4 (EP2D) and variant 5 (EP2E) appear to lack an exon, resulting in a shift in the open reading frame. Presumably, the 5 variants originate from the same gene and result from alternative promoters and alternative splicing. Each of the putative proteins encoded by these variant messages has a leader sequence characteristic for a secretory protein. After removal of the leader sequence, each of these proteins is predicted to consist of 1 or 2 out of 4 possible peptide modules. Two of these modules have no recognizable homology to known proteins. The other 2 modules have a distribution of cysteine residues characteristic for beta-defensins, a family of proteins with antimicrobial activity.
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PMID:Multiple promoter and splicing mRNA variants of the epididymis-specific gene EP2. 1081 50

HE2, a gene expressed specifically in human epididymis, gives rise to multiple mRNAs that encode a group of small cationic secretory peptides. Localization of HE2 within the defensin gene cluster and prediction that beta-defensin-like modules exist suggest that these peptides have antimicrobial activity and represent components of the innate epithelial defense system of the epididymal duct. Reverse transcription-polymerase chain reaction analysis confirmed the occurrence of eight human HE2-derived transcripts, including minor mRNA variants, that had previously been shown only in animal species. Employing isoform-specific antibodies against the predicted HE2 products, multiple 4- to 8-kDa peptides were detected in human epididymal epithelium, epididymal fluid, and ejaculate. N-terminal microsequencing has suggested a proteolytic processing of these peptides by a furin-like proprotein convertase, which cleaves a propiece from the longer precursor peptides. HE2alpha and HE2beta1, representing major peptide isoforms in the human epididymis, were recombinantly expressed, and their susceptibility to furin cleavage was demonstrated in vitro and in vivo. Processed recombinant peptides and chemosynthetic fragments were included in antimicrobial tests. In addition to the beta-defensin-like HE2beta1 with its expected antibacterial function, HE2alpha C-terminal fragments showed antibacterial activity against Escherichia coli, although it showed no significant similarity to beta-defensins nor to any other known protein family.
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PMID:Novel antimicrobial peptide of human epididymal duct origin. 1219 88

Vasectomy has been shown to affect the pattern of mRNA expression of P34H, a human sperm protein added to the acrosomal cap during epididymal transit. It has been reported that vasectomy alters the histology of the reproductive tract in various species as a result of the increased pressure in the epididymis. The aim of this study was to evaluate if other epididymis-specific mRNAs, which are expressed in different patterns along the duct, are altered by vasectomy as well. We analyzed the expression of P31m (a monkey homologue of human P34H) and three different HE-like (HE-l) mRNAs along the epididymis in the cynomolgus monkey (Macaca fascicularis). Sexually mature cynomolgus monkeys were vasectomized unilaterally; then the epididymides were surgically removed at different time points. The ipsilateral normal epididymis was used as a control. Histomorphometric measurements showed that the height of the epididymal epithelial cells started to be affected only at 14 wk postsurgery. However, Northern blot and in situ hybridization analysis showed that the expression pattern of P31m, HE1, and HE5-like mRNA along the epididymis was not affected by vasectomy. Only the HE2-like mRNA predominantly expressed in the normal corpus epididymidis was significantly lowered 14 wk after vasectomy. Thus, ductal obstruction differentially alters mRNA expression along the epididymis of the cynomolgus monkey.
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PMID:Effect of vasectomy on gene expression in the epididymis of cynomolgus monkey. 1260 26

The plasma membrane of spermatozoa undergoes substantial remodeling during passage through the epididymal duct, principally because of changes in phospholipid composition, exchange of glycoproteins with epididymal fluid, and processing of existing membrane proteins. Here, we describe the interaction of an epididymal glycoprotein recognized by monoclonal antibody 2D6 with the plasma membrane of rat spermatozoa. Our goals have been to understand more about the mechanism of secretion of epididymal glycoproteins, how they interact with the sperm's plasma membrane, and their disposition within it. Reactivity to 2D6 monoclonal antibody was first detectable in principal cells in the distal caput epididymidis and as a soluble high-molecular-weight complex in the secreted fluid. It was not associated with membranous vesicles in the duct lumen. On cauda spermatozoa 2D6 monoclonal antibody recognized a 24-kDa glycoprotein (the subunit of a disulfide cross-linked homodimer of 48 kDa) that was present on the plasma membrane overlying the sperm tail. Binding of 2D6 to immature spermatozoa in vitro was cell-type specific but not species specific, and the antigen could only be extracted from cauda spermatozoa with detergents. Sequencing studies revealed that the 24-kDa glycoprotein was a member of the beta-defensin superfamily of small pore-forming glycopeptides of which several others (ESP13.2, Bin1b, E-2, EP2, HE2) are found in the epididymis. This evidence suggests that some epididymal glycoproteins are secreted into the luminal fluid in a soluble form and bind to specific regions of the sperm's surface via hydrophobic interactions. Given the antimicrobial function of beta-defensins, they have a putative role in protecting spermatozoa and the epididymis from bacterial infections.
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PMID:Secreted epididymal glycoprotein 2D6 that binds to the sperm's plasma membrane is a member of the beta-defensin superfamily of pore-forming glycopeptides. 1289 Jul 30

Epididymal roles include protection and transport, maturation, and storage of the sperm cells. It is known that these functions are altered under vasectomy, but the consequences of excurrent duct obstruction on the pattern of gene expression along the human epididymis are poorly documented. In order to understand how excurrent duct occlusion affects different epididymal regions, the expression pattern of genes known to be expressed in specific epididymal segments was investigated along the epididymides of vasectomized men. Selected human epididymal complementary DNAs (cDNAs) identified by differential library screening were studied because of their unique messenger RNA (mRNA) distribution along the different epididymal segments. In situ hybridization as well as immunohistologic studies were undertaken to investigate the effect of vasectomy on a gene expressed all along the epididymis (HE1) or more selectively in the proximal (HE2) or distal (HE5) segment. The HE1 transcript was affected by the obstruction of the epididymis with little or no mRNA detectable along the epididymis. The HE1-related antigen was shown by immunohistochemical methods to be reduced within the epithelium of the epididymis of vasectomized men. By contrast, HE5 mRNA and protein, expressed in epithelial cells of the distal epididymis, were not affected by the obstruction of the vas deferens. Similarly, HE2 transcriptional and translational products normally expressed in the caput epididymidis were not affected by vasectomy. These results show that excurrent duct obstruction differentially affects the expression pattern of some specific transcripts and their encoded proteins, probably impairing their fundamental roles in the physiology of the epididymis.
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PMID:Vasectomy influences expression of HE1 but not HE2 and HE5 genes in human epididymis. 1466 84

Beta-defensins are small cationic peptides exhibiting broad spectrum antimicrobial properties. In humans, many beta-defensin genes are located within a cluster on chromosome 8p23. The sperm associated antigen 11 (SPAG11) gene is contained in this cluster and is unusual among the human beta-defensins due to its complex genomic structure and mRNA splicing pattern. Here we report the genomic organization of the Bos taurus SPAG11 gene located on chromosome 27q1.2, within a cluster of beta-defensin genes. The exon structures of the fused bovine SPAG11 gene and of the mosaic transcripts initiated at both A and B promoters were established, including identification of novel exons and transcripts not previously found in primate or rodent. Evolutionary analysis against primate, rodent, canine, and porcine orthologs was performed. In adult bulls SPAG11C, SPAG11E, and SPAG11U mRNAs were detected predominantly in the male reproductive tract, while SPAG11D transcript was detected in reproductive and nonreproductive tissues and SPAG11V and SPAG11W mRNAs were confined to testis. Differential expression of all six transcripts was observed in tissues from fetal and adult bulls, suggesting that similar mRNA splicing mechanisms govern SPAG11 gene expression during pre- and postnatal development. Immunolocalization of SPAG11C and SPAG11D/E was demonstrated in the epithelium of the epididymis and testis, and SPAG11D in association with epididymal spermatozoa. Recombinant full-length SPAG11D protein was strongly antibacterial, while the SPAG11E C-terminal peptide that contains the beta-defensin motif in its structure was somewhat less potent. Taken together, the results suggest that SPAG11 isoforms perform both immune and reproductive functions in cattle.
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PMID:Novel aspects of the sperm-associated antigen 11 (SPAG11) gene organization and expression in cattle (Bos taurus). 1734 69


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