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)

The amino acid sequence of a major human epididymis-specific protein was deduced from the nucleotide sequence of its cloned cDNA. The encoded product showed characteristics of a secretory protein, with a signal peptide followed by a small (approximately 10-kDa), acidic (pI 4.3), and cysteine-rich polypeptide. The positions of half-cysteines suggested that it was a two-domain member of the family of 'four-disulfide core' proteins to which a number of proteinase inhibitors belong. Southern blot analyses of human genomic DNA showed that the transcripts originated from a single copy gene. Northern blot and in situ transcript hybridization specifically localized the HE4 (human epididymis gene product) mRNA to the epithelial cells of the epididymal duct, predominantly within the distal sections. A possible function in sperm maturation as indicated by amino acid similarities to extracellular proteinase inhibitors of genital tract mucous secretions is discussed in the context of its tissue-specific transcription.
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PMID:A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. 168 87

The physiology of the epididymis is an integral part of the maturation process by which human spermatozoa acquire the ability to reach and fertilize an oocyte. Because of the high degree of species specificity exhibited by the epididymal proteins involved in sperm maturation, we have assessed tissue from several alternative species for their suitability as a model for human epididymal physiology. Of these, the dog appears to offer an appropriate system. Northern hybridization using cDNA probes specific for human epididymal genes established that, irrespective of dog breed, the canine equivalents of the epididymis-specific HE1, HE4 and HE5 mRNAs were expressed highly in the canine epididymis. cDNA cloning and sequencing confirmed that the canine gene products, CE1, CE4 and CE5 were indeed true structural homologues of their human counterparts. Finally, tissue culture conditions were established wherein all three specific canine genes remained up-regulated after 5 days of culture. Thus, the prerequisite criteria for the development of a system which models human epididymal physiology are to a large degree fulfilled by this canine culture system.
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PMID:Gene expression in the dog epididymis: a model for human epididymal function. 774 11

In-situ transcript hybridization was used to characterize the regional distribution of three marker gene transcripts which are expressed abundantly in the canine epididymis. The gene products CE1, CE4 and CE5, which are the canine equivalents of the human homologues HE1, HE4 and HE5, are shown to be expressed in a tissue-specific and regionally characteristic pattern in the epididymal epithelium. CE1 mRNA was expressed very weakly in the efferent ducts but was expressed at a high level throughout the caput and corpus regions of the epididymis, decreasing somewhat in the distal cauda region. CE4 mRNA was not detectable in the efferent ducts and was only expressed moderately in the remainder of the epididymis, with greatest levels in the caput and proximal cauda regions, and decreasing in the distal cauda. CE5 mRNA showed the most marked regional variation in levels with little or no mRNA detectable in the caput and proximal corpus regions, but increasing dramatically in the distal corpus and cauda. In the transition region of the central corpus, the CE5 mRNA appeared to be expressed intermittently, giving a mottled signal appearance over the epididymal epithelium. The patterns of mRNA distribution for the three marker genes in the dog epididymis were, therefore, essentially similar to those for the equivalent human homologues, providing further support for the suitability of the dog epididymis as a model for the human.
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PMID:Regional variation of specific gene expression in the dog epididymis as revealed by in-situ transcript hybridization. 774 12

cDNA probes derived from genes expressed specifically in the human epididymis were used to examine gene expression in the epididymides of boar, bull and stallion by Northern hybridization. Two probes for the HE1 and HE4 gene products were found to recognize tissue-specific transcripts in all three species, with a regionally differential distribution within the epididymis. Additionally, antibodies recognizing the HE4 protein were shown to react specifically in the epididymis of the boar and bull. An extensive study of the boar showed that, whereas mRNA for the HE1-homologue was up-regulated markedly only at puberty, the HE4-homologue was already present at moderate levels prepubertally. The distribution of the HE1-homologue changed at sexual maturity from a maximum in the cauda epididymis in the 3-4-week-old pig, to a maximum in the corpus/caput region in the adult, while the shift was in the opposite direction for the HE4-homologue. Evidently, gene expression is not fixed regionally through epididymal development in this species. The abdominal epididymis of a hemicryptorchid pig also showed a differential change in expression for the two gene products by comparison with the scrotal testis from the same animal. The results suggest that the HE1 and HE4 gene homologues may be sensitive markers for physiological changes within the mammalian epididymis, and that the boar could prove a useful model to examine the regulation of these human epididymal transcripts.
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PMID:Tissue-specific gene expression as an indicator of epididymis-specific functional status in the boar, bull and stallion. 809 31

A protein designated as BE-20 was purified from cauda epididymal fluid of the rabbit by preparative polyacrylamide gel electrophoresis and HPLC on a mono Q HR5/5 anion exchange column. The purified protein migrated with an estimated Mt of 20,000 when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The amino acid sequence of the N-terminus of the BE-20 protein was determined. The initial eight amino acid residues were His-Gly-Ala-Asp-Lys-Pro-Gly-Val. The corresponding 23 mer oligonucleotide (5'-CATGGCGCTGACAAGCCTGGGGT-3') was synthesized and used as sense primer with rabbit epididymal mRNA as template in the RT-PCR system. The purified BE-20 cDNA consisted of 499 bp with an open reading frame of 285 bp encoding a deduced polypeptide composed of 95 amino acids. The BE-20 cDNA had 78.5% identity in 479 bp overlap with human epididymis-specific HE4 cDNA. The amino acid sequences of the initial 30 amino acid residues of the N-terminus of the purified protein and the deduced polypeptides were as follows: N-His-Gly-Ala-Asp-Lys-Pro-Gly-Val-Cys-Pro-Gln-Leu-Ser-Ala-Asp-Leu-Asn-Cy s- Thr-Gln-Asp-Cys-Arg-Ala-Asp-Gln-Asp-Cys-Ala-Glu. The deduced polypeptide contained 16 cysteine residues and had partial sequence homology with proteins belonging to the four-disulfide core family of extracellular proteinase inhibitors. The BE-20 protein may play a role in sperm maturation and/or capacitation.
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PMID:Identification of a rabbit epididymal protein gene. 888 63

Sperm maturation depends on androgen and is mediated by several unidentified epididymal factors: glycoproteins and metabolites affecting acrosomal stability and fertilizing potential of capacitated sperm. Several genes encoding human epididymis-specific proteins have been described. One of the cloned epididymal cDNA encodes a polypeptide designated as HE4 with an estimated molecular mass of 10,000. Leydig cells are rich in lipid droplets and display epithelioid features. These cells have a cord-like arrangement; the cords are formed by one or two closely apposed cells. In between these cells, labyrinthine or canalicular-like spaces are opened in wide perivascular spaces that improve cell secretion of hormones and facilitate their transport into the blood, as well as the traffic of fluids and metabolites. Coagulation and liquefaction in human semen plays an important role in the capacitation of semen. The liquefaction of semen is retarded by the powerful synthetic inhibitors of 6-amidino-2-naphtyl-p-guanidinobenzoate dimethansulfonate.
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PMID:Recent advances in andrology research: physiopathology and clinical application to fertility and infertility. 935 30

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 truncated cDNA coding a rabbit epididymal protein (BE-20) was identified in a previous study. In the present study the full-length cDNA was isolated by the method of rapid amplification of cDNA ends. The BE-20 cDNA consisted of 585 bp with a poly(A) tail of 26 residues and an open reading frame composed of 369 bp encoding a deduced polypeptide containing 123 amino acid residues with a calculated molecular mass of 13 kDa. The N-terminus-contained a leucine-rich segment. BE-20 cDNA has about 76.8% homology with the HE4 gene of human epididymis. Northern blot analysis of mRNAs prepared from 17 different human tissues was performed using as probe a 0.5-kb DNA fragment corresponding to a segment of BE-20 cDNA. Positive reaction was elicited only with epididymal mRNA. A DNA fragment corresponding to a section of the open reading frame of BE-20 cDNA was cloned in Escherichia coli under the control of the T7 promoter. The cellular content of the expressed recombinant protein comprised about 55% of the total protein. The chromatographically purified bacterial product migrated as a single band with an estimated M(r) of 15 kDa on analysis by SDS-PAGE. In conclusion, BE-20 cDNA is expressed only in the epididymis. It is structurally related to the four-disulfide core family of extracellular proteinase inhibitors and may be involved in sperm maturation.
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PMID:Expression and characterization of an epididymis-specific gene. 1010 72

Primary cultures of the differentiated, adult epididymal duct epithelium were immortalized by retroviral transduction with the simian virus (SV)40 large T antigen. The canine epididymis was chosen here as a model with high human relevance, representing a convenient and acceptable source of differentiated epididymal tissue and, compared to other animal models, expressing a relatively large number of gene products which are also expressed by the human epididymis. To determine whether the immortalized canine epididymal (IMCE) cells retained a phenotype comparable to the original tissue, epithelial cytokeratins, various epididymal transcription factors as well as mRNAs encoding abundant epididymal secretory proteins, were studied as molecular markers. All IMCE populations obtained after transduction were of epithelial origin. The nuclear androgen receptor (AR) and the polyoma enhancer activator (PEA3), as well as the epididymal mRNA encoding the canine counterparts of human HE1, HE4 and HE5/CD52 epididymal mRNA, were retained in all populations tested. The majority of tested clones were oestrogen receptor ERalpha-positive, but ERbeta-negative, while one ERalpha-negative cell population was positive for ERbeta. The IMCE populations described thus represent useful permanent tools for studying gene expression of the epididymal duct epithelium, and for other types of experiments, examples including drug effects and toxicity on the epididymis.
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PMID:Epididymal epithelium immortalized by simian virus 40 large T antigen: a model to study epididymal gene expression. 1157 62

Northern blot analysis suggested that the boar epididymis produces closely related counterparts to human epididymal proteins HE1, HE3, HE4, HE5 and HE12. 'Full-length' cloning by nucleic acid and amino acid sequence similarity was achieved by RT-PCR methods in the case of the porcine counterparts of HE3 and HE4, while the homologues of HE5 and HE12, despite their cross-hybridization during Northern blot analysis, have not yet been cloned. The two novel porcine cDNAs were derived from moderately abundant epididymal mRNAs that were 75 and 83% identical to HE3 and HE4 cDNAs, respectively. To emphasize their relationship to the corresponding HEs, they were named Se3 and Se4 cDNAs. Their open reading frames predicted small secretory proteins with 55% (Se3) and 76% (Se4) conserved amino acids. Monospecific antipeptide antibodies to HE secretory proteins identified He3- and HE12-related proteins on Western blots of porcine epididymal fluid and semen. Both Northern and Western analyses indicated that the Se proteins were produced in a regionalized pattern and accumulated in the cauda fluid.
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PMID:Cloning and characterization of boar epididymal secretory proteins by homology to the human. 1265 21


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