Biomedical subjects

Y Hort

Publications and source records attributed to Y Hort.

8 recordsLinked to original sources

PubMed1997

Overlapping gene structure of the human neuropeptide Y receptor subtypes Y1 and Y5 suggests coordinate transcriptional regulation.

The human y1 and y5 receptor genes are transcribed in opposite directions from a common promoter region on chromosome 4q31-q32. One of the alternately spliced 5' exons of the y1 receptor gene (1C) is also an integral part of the coding region of a novel neuropeptide Y receptor, Y5. Exon 1C of the y1 receptor gene, if translated from the opposite strand, encodes sequences corresponding to the large third intracellular loop of the Y5 receptor. The close proximity of the two neuropeptide Y receptor genes suggests that they have evolved from a gene duplication event with the small intron interrupting the coding sequence of the y1 gene being converted into a functional sequence within the y5 gene, while the reverse complementary sequence was utilized as an alternatively spliced 5' exon for the y1 gene. The transcription of both genes from opposite strands of the same DNA sequence suggests that transcriptional activation of one will have an effect on the regulation of gene expression of the other. As both Y1 and Y5 receptors are thought to play an important role in the regulation of food intake, coordinate expression of their specific genes may be important in the modulation of NPY activity.

Alternative Splicing↗

PubMed1995

Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1.

Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related but functionally diverse peptides, encoded by separate genes and expressed in different tissues. Although the human NPY gene has been mapped to chromosome 7, we demonstrate here that the genes for human PYY and PP (PPY) are localized only 10 kb apart from each other on chromosome 17q21.1. The high degree of homology between the members of this gene family, both in primary sequence and exon/intron structure, suggests that the NPY and the PYY genes arose from an initial gene duplication event, with a subsequent tandem duplication of the PYY gene being responsible for duplication of the PYY gene being responsible for the creation of the PPY gene. A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event.

Amino Acid Sequence↗

PubMed1995

Seminalplasmin: recent evolution of another member of the neuropeptide Y gene family.

Seminalplasmin, the major basic protein of bull semen, an important regulator of calcium transport in bovine sperm and a positive modulator of the zona pellucida-induced acrosome reaction, is shown to be a recently created member of the neuropeptide Y gene family. Sequence analysis of the bovine peptide YY-pancreatic polypeptide gene cluster reveals an unexpected and extensive homology between seminalplasmin and the neuropeptide Y gene family, at the level of both gene structure and primary amino acid and nucleotide sequences. The extremely high degree of homology to the peptide YY gene, in both coding and especially noncoding regions, suggests that the seminalplasmin gene has arisen by a very recent gene duplication of the bovine peptide YY gene. Despite the more than 95% nucleotide sequence identity, a few specific mutations in the seminalplasmin gene have resulted in both the loss of the amino- and carboxyl-terminal cleavage sites characteristic of all other members of the neuropeptide Y family and the acquisition of a function apparently unrelated to the neurotransmitter/endocrine role of peptide YY.

Amino Acid Sequence↗

PubMed1988

Isolation, structure and expression of cDNA and genomic clones for murine eosinophil differentiation factor. Comparison with other eosinophilopoietic lymphokines and identity with interleukin-5.

Eosinophil differentiation factor (EDF) is a recently described regulator affecting eosinophil growth and activation. cDNA clones for murine EDF were isolated by direct expression from libraries prepared from the T cell hybrid NIMP-TH1. The longest cDNA clone obtained was 1534 bp in length encoding a polypeptide of 133 amino acids. Two variant cDNAs suggesting alternative RNA processing events were detected. The EDF gene was cloned from a genomic lambda library and a region of 6727 bp encompassing the gene was sequenced. The gene contains three introns 829, 1875 and 79 bases in length and has numerous repetitive sequences. A common, possible regulatory element, including a conserved decamer, lies adjacent to the TATA boxes of the EDF and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes and similar sequences are present in some other lymphokine genes. Recombinant EDF produced in monkey COS cells strongly stimulated the eosinophil lineage and also showed B-cell-growth factor II (BCGFII) activity whereas recombinant murine interleukin-3 and GM-CSF showed much broader activity towards the different myeloid lineages, were less active on eosinophils and had no BCGFII activity. The BCGFII activity of recombinant EDF together with a comparison of the BCGFII (interleukin-5) cDNA sequence with that of the EDF cDNA establishes that these two activities are the properties of a single polypeptide.

Animals↗

PubMed1987

Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5).

The human eosinophil differentiation factor (EDF) gene was cloned from a genomic library in lambda phage EMBL3A by using a murine EDF cDNA clone as a probe. The DNA sequence of a 3.2-kilobase BamHI fragment spanning the gene was determined. The gene contains three introns. The predicted amino acid sequence of 134 amino acids is identical with that recently reported for human interleukin 5 but shows no significant homology with other known hemopoietic growth regulators. The amino acid sequence shows strong homology (approximately 70% identity) with that of murine EDF. Recombinant human EDF, expressed from the human EDF gene after transfection into monkey COS cells, stimulated the production of eosinophils and eosinophil colonies from normal human bone marrow but had no effect on the production of neutrophils or mononuclear cells (monocytes and lymphoid cells). The apparent specificity of human EDF for the eosinophil lineage in myeloid hemopoiesis contrasts with the properties of human interleukin 3 and granulocyte/macrophage and granulocyte colony-stimulating factors but is directly analogous to the biological properties of murine EDF. Human EDF therefore represents a distinct hemopoietic growth factor that could play a central role in the regulation of eosinophilia.

Amino Acid Sequence↗

PubMed1986

Sequence and expression of human estrogen receptor complementary DNA.

The mechanism by which the estrogen receptor and other steroid hormone receptors regulate gene expression in eukaryotic cells is not well understood. In this study, a complementary DNA clone containing the entire translated portion of the messenger RNA for the estrogen receptor from MCF-7 human breast cancer cells was sequenced and then expressed in Chinese hamster ovary (CHO-K1) cells to give a functional protein. An open reading frame of 1785 nucleotides in the complementary DNA corresponded to a polypeptide of 595 amino acids and a molecular weight of 66,200, which is in good agreement with published molecular weight values of 65,000 to 70,000 for the estrogen receptor. Homogenates of transformed Chinese hamster ovary cells containing a protein that bound [3H]estradiol and sedimented as a 4S complex in salt-containing sucrose gradients and as an 8 to 9S complex in the absence of salt. Interaction of this receptor-[3H]estradiol complex with a monoclonal antibody that is specific for primate ER confirms the identity of the expressed complementary DNA as human estrogen receptor. Amino acid sequence comparisons revealed significant regional homology among the human estrogen receptor, the human glucocorticoid receptor, and the putative v-erbA oncogene product. This suggests that steroid receptor genes and the avian erythroblastosis viral oncogene are derived from a common primordial gene. The homologous region, which is rich in cysteine, lysine, and arginine, may represent the DNA-binding domain of these proteins.

Amino Acid Sequence↗

PubMed1984

Human renin gene sequence, gene regulation and prorenin processing.

Human DNA coding for renin was identified and sequenced. The gene consisted of 10 exons corresponding to a 1500 nucleotide mRNA was broken up by long stretches of 'nonsense' DNA (introns) and spanned 12,000 base pairs. In addition, the sequence of nucleotides involved in regulation of the gene was determined by sequencing upstream. Prediction of the amino acid sequence of human preprorenin revealed likely sites of processing. This helps explain many past experimental observations. For example, the pro region contained adjacent likely cleavage sites for trypsin and pepsin and so reveals why both trypsin and pepsin can activate prorenin. The structure of human renin had features involved in its highly specific hydrolysis of the Leu10-Val11 bond unique to human angiotensinogen: in particular leucine 224 (instead of valine). Renin gene expression was studied in the mouse by quantification of both renin activity and its mRNA. Sodium depletion, captopril and spironolactone increased expression of Ren-1 in the kidney. The unusual, duplicated, mouse gene, Ren-2, which is expressed in the submandibular gland was, regulated by (dihydro)testosterone in male mice and by thyroid hormone in female mice.

Animals↗

PubMedDate not supplied

Structure of human renin and expression of the renin gene.

The amino acid sequence of human renin was identified for the first time. This was determined from the nucleotide sequence of exons in the human renin gene identified in a genomic library by recombinant DNA techniques. Examination of amino acid residues involved in the enzymatic hydrolysis by human renin of the unique Leu10-Val11 bond of human angiotensinogen revealed features peculiar to this highly specialized aspartyl protease. The expression of the renin gene was examined with a hybridization probe for renin mRNA in sections and extracts of tissues. In the submandibular gland of mice renin mRNA, like renin, increased during development and in response to testosterone in females; sodium depletion increased renin mRNA in kidney.

Amino Acid Sequence↗