Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene CREM plays key physiological and developmental roles within the hypothalamic--pituitary--gonadal axis. We have previously shown that CREM is highly expressed in male postmeiotic cells. Spermiogenesis is a complex process by which postmeiotic male germ cells differentiate into mature spermatozoa. CREM regulates the expression of a number of post-meiotic genes involved in the process of spermiogenesis. Using homologous recombination we have generated CREM-mutant mice that display a complete block at the first step of spermiogenesis. The molecular mechanism by which CREM elicits its regulatory function involves ACT (Activator of CREM in Testis), a testis-specific coactivator constituted by a repeat of four and half LIM domains. ACT is coordinately expressed with CREM, associates with it and confers a powerful transcriptional activation function. It is able to bypass the classical requirement of CREM phosphorylation and recruiting of CBP.
Mol Cell Endocrinol 2001 Jun 20
PMID:Transcriptional cascades during spermatogenesis: pivotal role of CREM and ACT. 1142 Jan 26

A differential display-polymerase chain reaction was employed to obtain a testis-specific cDNA fragment. On screening the human testis-(lambda)gt10-cDNA library with testis-specific cDNA fragment, a novel cDNA encoding for a sperm antigen, designated TSA-1, was obtained. It has a novel open reading frame (ORF) of 471 base pairs encoding for 156 amino acids. The computer generated translated protein has a calculated molecular mass of 17.4 kDa and contains a potential N-glycosylation site at amino acids 122-124. The hydrophilicity analysis of the amino acid sequence suggested that this protein is a membrane-anchored peptide. Extensive analysis for tissue-specificity by Northern blots and RT-PCR-Southern blot procedures using various human tissues indicated that TSA-1 was specifically expressed only in the human testis. Based on the results of in vitro transcription and translation experiments, the TSA-1 (ORF) was subcloned into pGEX-6P-3 vector and expressed using the glutathione S-transferase gene fusion system. Antibodies (Ab) against the purified recombinant protein specifically recognized the approximately 17 kDa recombinant TSA-1, and a approximately 24 kDa band in human sperm extract in the Western blot procedure. The recombinant TSA-1 Ab recognized the acrosomal, equatorial, mid-piece, and tail regions of human sperm cell in indirect immunofluorescence, bound to live human sperm in the immunobeads binding technique (IBT) and caused a significant concentration-dependent inhibition of human sperm acrosome reaction. These findings indicate that the novel sperm-specific recombinant TSA-1 has a role in sperm function and may have applications in the development of a contraceptive vaccine, and in the specific diagnosis and treatment of male infertility.
Mol Reprod Dev 2001 Sep
PMID:Novel human testis-specific cDNA: molecular cloning, expression and immunobiological effects of the recombinant protein. 1155 Feb 62

Sperm-specific antigens are attractive candidates for the development of a contraceptive vaccine. Using the subtractive cDNA hybridization technology, the present study was conducted to obtain a human sperm-specific antigen. The 32P-labeled single stranded cDNA of human testis, subtracted with poly(A)+ RNA of human peripheral white blood cells, was used to screen the human testis cDNA-ZAP II library. The putative positive clones were further screened for binding with the solubilized human oocyte zona pellucida preparation (HZP). After screening 10(7) colonies, one positive clone, designated contraceptive vaccinogen (CV), was obtained. It had an insert of approximately 1.3 kb, that was cloned and sequenced. The sense strand was identified by using the in vitro transcription and translation procedures, and the full-length sequence was obtained by using the 5' rapid amplification of 5' -cDNA ends (5'-RACE) procedure. The full-length CV cDNA has an ORF of 312 amino acids (aa) with the first ATG Met start codon at nucleotide (nt) 35 and the stop codon TAA, at nt 959. The translated protein has a calculated molecular mass of 35.3 kD and four potential N-linked glycosylation and several phosphorylation sites. Hydropathy plot generated from the deduced aa sequence showed it to be a membrane-anchored peptide. Extensive computer search in the database did not find any homology of existing sequences with CV both for nt and aa. Northern blot analysis indicated the human testis-specific expression of CV antigen. The coding region of CV cDNA was subcloned into pET22b(+) vector and expressed. The expressed recombinant (r)CV protein had a molecular size of approximately 44 kD, and it specifically reacted with the ZP3 component of HZP. Rabbit rCV antibodies recognized the rCV, and a cognate antigen of approximately 64 kD in the human sperm extract. The antibodies showed binding with the live and methanol-fixed human sperm, and significantly (P < 0.001) inhibited human sperm penetration of zona-free hamster oocytes, as well as human sperm binding to human oocyte zona pellucida. These findings indicate that the testis/sperm- specific CV antigen has a role in human sperm function and may find clinical applications in the contraceptive vaccine development and in the specific diagnosis and treatment of male infertility.
Mol Reprod Dev 2001 Sep
PMID:Cloning and sequencing of cDNA encoding for a novel human testis-specific contraceptive vaccinogen: role in immunocontraception. 1155 Feb 75

Previously, we identified a partial cDNA sequence of a novel human transcript, designated fetal and adult testis expressed transcript (FATE). FATE is testis-specific in fetal life and co-expressed with SRY in a 7 weeks old fetal testis, suggesting a function in early testicular differentiation. Herein, full-length cDNA clones of human and porcine FATE were isolated and the gene structure and promoter region of the human FATE gene was characterized. The human FATE gene, which maps to Xq28, consists of five exons spanning approximately 7 kb of genomic DNA. Examination of 1 kb of the FATE promoter region revealed the presence of a putative steroidogenic factor 1 (SF-1) binding site at position -79 to -71 upstream of the transcription start site. We propose that FATE might represent a novel target gene of SF-1 in human testicular differentiation and/or germ cell development.
Mol Cell Endocrinol 2001 Nov 26
PMID:Human FATE is a novel X-linked gene expressed in fetal and adult testis. 1169 38

Succinyl CoA: 3-oxo acid CoA transferase (scot; EC 2.8.3.5) is a key enzyme for metabolism of ketone bodies. Previously, we have cloned a testis-specific succinyl CoA: 3-oxo acid CoA transferase (scot-t) cDNA from a subtracted cDNA library of mouse testis and demonstrated its expression to be specific to late haploid male germ cells. In this study, the human orthologue of mouse scot-t was cloned and characterized. The entire coding region of the mRNA and the deduced amino acid sequence of human Scot-t (h-Scot-t) showed 75.4 and 75.8% identity with mouse scot-t respectively. The mRNA was exclusively expressed in the testis, and the protein was localized to the midpiece of ejaculated spermatozoa where mitochondria exist. We showed that the h-Scot-t gene was intronless by using a polymerase chain reaction technique and that a non-functional pseudogene, 98% similar to h-Scot-t, was also located on the human genome (1p33-34.3). Furthermore, the genomic structure of the actual h-Scot-t transcription unit was found to be located in an intron (1p34.1-35.3) of the bone morphogenetic protein 8 (BMP8) gene. In conclusion, we have demonstrated that h-Scot-t is a single intronless gene specifically expressed in the testis.
Mol Hum Reprod 2002 Jan
PMID:Cloning and characterization of a human orthologue of testis-specific succinyl CoA: 3-oxo acid CoA transferase (Scot-t) cDNA. 1175 65

A human testis-specific gene was isolated by subtractive hybridization between the cDNA pools of adult and fetal testes, followed by rapid amplification of cDNA ends (RACE). This gene sequence is highly homologous to a large portion of the mouse Tcp11 gene which is important in sperm function because it encodes the receptor for fertilization-promoting peptide (FPP). The gene was mapped to human chromosome band 6p21 by fluorescence in-situ hybridization. The 9 exon gene spans a 22.8 kp genomic DNA sequence. The mature processed message encodes a 441 amino acid protein that is highly homologous to the mouse 566 amino acid protein after the first 142 amino acids. Results of Northern blot and RT-PCR analyses of RNA extracted from human tissues revealed that the gene is only expressed in fertile adult testes, but not in azoospermic testes, fetal testes nor in other human tissues. Taken together, our results along with the mouse Tcp11 function suggest that TCP11 gene is important in sperm function and fertility.
Mol Hum Reprod 2002 Jan
PMID:Molecular characterization of the TCP11 gene which is the human homologue of the mouse gene encoding the receptor of fertilization promoting peptide. 1175 66

A 1933 bp cDNA fragment, coding a truncated testis-specific novel nucleoporin, was isolated from a human testis lambdaZAPII cDNA library, designated as BS-63 and assigned GenBank accession number: U64675. By applying the methods of rapid amplification of cDNA ends (5' RACE) and PCR, a full-length BS-63 cDNA composed of 5475 bp was obtained. BS-63 cDNA contained an open reading frame consisting of 1765 codons and XFXFG or GLFG repetitive sequence motifs. These repetitive motifs are structural characteristic of nucleoporins. BS-63 cDNA has high homology with Nup358/Ran BP2. A 1599 bp fragment, corresponding to the C-terminus of BS-63 cDNA, was prepared and expressed in E. coli BL21(DE3). The recombinant product was purified by affinity chromatography and SDS-PAGE and polyclonal antibodies raised. In rat testis section, the BS-63 protein was localized at the sites of nuclear pores in spermatids by immuno-gold transmission electron microscopy and on the nuclear membrane of Triton X-treated sperm by colloidal silver immuno-gold scanning electron microscopy. The recombinant BS-63 protein can be phosphorylated in vitro with PKC and p34(cdc2). A yeast two-hybrid system was used to screen a mouse testis cDNA library to identify proteins capable of interacting with BS-63. Using the 1.6 kb cDNA fragment as bait, the following interacting proteins were identified: Ran, transportin (karyopherin beta2), two proteins related to the nucleocytoplasmic transporter and aF10 protein. The latter protein is a putative transcriptor containing a cysteine-rich N-terminus, a LAP/PHD finger, a leucine zipper domain and a glutamine-rich C-terminus. Also it is highly expressed in murine testis and is located in the cell nucleus and cytoplasm. The interaction of BS-63 with aF10 (696-1001aa) was validated by surface plasmon resonance and by affinity precipitation combined with Western blot. aF10 (696-1001aa) interacted in vitro with BS-63 extracted from rat testis germ cells. It is hypothesized that BS-63 is a testis-specific nucleoporin and possibly acts as a docking site and a cotransporter of Ran and transportin. The complex performs the task of a carrier system in transporting aF10 into the nucleus of germ cells during spermiogenesis.
Mol Reprod Dev 2002 Jan
PMID:Characterization and potential function of a novel testis-specific nucleoporin BS-63. 1177 84

Angiotensin converting enzyme (ACE) is a membrane-bound dipeptidyl carboxy-peptidase that generates vasoconstricting angiotensin II and inactivates vasodilating bradykinin. The ACE gene encodes two isozymes: the somatic isozyme (sACE) is found in many tissues including vascular endothelial cells, whereas the testis-specific isozyme (tACE) is expressed exclusively in developing spermatids and mature sperm. Thus, ACE might have physiological functions in addition to blood pressure regulation. Male mice lacking tACE activity show reduced fertility, indicating its importance in male fertility. In this study, we screened five recently defined tACE gene polymorphisms in 90 Singapore Chinese men with infertility and 84 fertile controls using PCR-based restriction fragment length polymorphism and DNA sequencing. However, only one of these polymorphisms was identified in both patient and control groups, the frequency of which was not significantly different in patients and controls. Thus, these ACE gene polymorphisms are unlikely to contribute to the pathogenesis of male infertility in the Singapore Chinese population.
Mol Hum Reprod 2002 Mar
PMID:Lack of association between polymorphisms in the testis-specific angiotensin converting enzyme gene and male infertility in an Asian population. 1187 Feb 38

The presence of the 34-kDa hyaluronan binding protein 1 (HABP1) on sperm surface and its role in fertilization is already established (Ranganathan et al., 1994: Mol Reprod Dev 38:69-76). In the present communication, we examined the expression of HABP1 in adult rat testis during spermatogenesis. Interestingly, using anti-rHABP1 antibody, we detected a protein of 55 kDa which was present only in testis, but not in other somatic tissues like spleen and liver. However, even in testis, only one transcript of HABP1 mRNA of 1.63 kb was observed. In addition, we confirm that this testis-specific 55 kDa protein was immunologically identical with proprotein form of HABP1 using antibody raised against a decapeptide present in the proprotein region of HABP1. Comparative immunohistochemistry of testis, spleen, and liver tissues using both the antibodies supported the observation that the proprotein form of HABP1 is present only in testis. Higher mRNA expression of HABP1 in testis as compared to that of liver and spleen could be speculated from the RT-PCR product. Finally, detailed study of the immunohistochemical staining of the seminiferous tubules revealed the expression of the HABP1 proprotein in specific stages of germ cells, like pachytene spermatocytes and round spermatids, but not in elongated ones, suggesting a possible role of HABP1 proprotein in spermatogenic differentiation.
Mol Reprod Dev 2002 Jun
PMID:Stage-specific expression of proprotein form of hyaluronan binding protein 1 (HABP1) during spermatogenesis in rat. 1198 33

Differentiating male germ cells express a testis-specific form of cytochrome c (Cyt c(T)) that is distinct from the cytochrome c expressed in somatic cells (Cyt c(S)). To examine the role of Cyt c(T) in germ cells, we generated mice null for Cyt c(T). Homozygous Cyt c(T)(-/-) pups were statistically underrepresented (21%) but developed normally and were fertile. However, spermatozoa isolated from the cauda epididymis of Cyt c(T)-null animals were less effective in fertilizing oocytes in vitro and contain reduced levels of ATP compared to wild-type sperm. Sperm from Cyt c(T)-null mice contained a greater number of immotile spermatozoa than did samples from control mice, i.e., 53.1% +/- 13.7% versus 33.2% +/- 10.3% (P < 0.0001) for vas deferens sperm and 40.1% +/- 9.6% versus 33.2% +/- 7.5% (P = 0.0104) for epididymal sperm. Cyt c(T)-null mice often exhibit early atrophy of the testes after 4 months of age, losing germ cells as a result of increased apoptosis. However, no difference in the activation of caspase-3, -8, or -9 was detected between the Cyt c(T)(-/-) testes and controls. Our data indicate that the Cyt c(T)-null testes undergo early atrophy equivalent to that which occurs during aging as a consequence of a reduction in oxidative phosphorylation.
Mol Cell Biol 2002 Aug
PMID:Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy. 1210 Dec 47


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