Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nonapeptide hormones arginine vasopressin (AVP) and oxytocin (OT) are synthesized in the hypothalamus together with their carrier proteins, the neurophysins, as common polypeptide precursors. The organization of these precursors has been established by sequence determination of cloned bovine cDNAs encoding prepro-arginine vasopressin-neurophysin II (prepro-AVP-NPII) and prepro-oxytocin-neurophysin I (prepro-OT-NPI). When the mRNA sequences coding for the conserved middle part of the neurophysins were compared, we found that these sequences are not merely similar but identical. The primary structure of the chromosomal genes now determined shows that both genes, which appear to have arisen by a gene duplication, are split into three exons, each encoding a functional domain of the precursor polypeptide. Sequence comparison reveals that the stretch of sequence identity within the two mRNAs is probably the result of a gene conversion encompassing exon B, which encodes the conserved part of the neurophysins, and part of the preceding intron.
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PMID:Recent gene conversion involving bovine vasopressin and oxytocin precursor genes suggested by nucleotide sequence. 670 64

We examined the nucleotide sequence of the arginine vasopressin-neurophysin II gene in three kindreds with autosomal dominant neurohypophyseal diabetes insipidus. Each of the three different mutations identified represents a recurrence of a mutation previously described to cause this disease. These mutations are all transitions (C1761-->T, G1859-->A, and G279-->A) that encode amino acid substitutions Pro24-->Leu, Gly57-->Ser (both in neurophysin II), and Ala-->Thr (in the last amino acid at the C-terminus of the signal peptide). The presence of these mutations in genomic DNA was confirmed by alterations in restriction endonuclease recognition sites. A linkage map of distal chromosome 20 was constructed. To examine the possibility that these apparent recurrent mutations arose independently rather than by an ancestral founder mutation, we analyzed family origins, two polymorphic markers on chromosome 20 in close proximity with this gene (the oxytocin/XbaI restriction fragment length polymorphism and the D20S57 polymorphic CA repeat microsatellite), and/or the occurrence of a de novo mutation in our three families and in four additional families previously reported. Our results suggest that one of our families may share an ancestral founder mutation with one previously reported family, but that in the remainder of the families with identical mutations, these mutations probably arose independently.
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PMID:Recurrent mutations in the vasopressin-neurophysin II gene cause autosomal dominant neurohypophyseal diabetes insipidus. 896 72

The objective of this study is to identify the genetic defects in a Chinese family with autosomal dominant familial neurohypophyseal diabetes insipidus. Complete physical examination, fluid deprivation, and DDAVP tests were performed in three affected and three healthy members of the family. Genomic DNA was extracted from leukocytes of venous blood of these individuals for polymerase chain reaction amplification and direct sequencing of all three coding exons of arginine vasopressin-neurophysin II (AVP-NPII) gene. Seven members of this family were suspected to have symptomatic vasopressin-deficient diabetes insipidus. The water deprivation test in all the patients confirmed the diagnosis of vasopressin-deficient diabetes insipidus, with the pedigree demonstrating an autosomal dominant inheritance. Direct sequence analysis revealed a novel mutation (c.193T>A) and a synonymous mutation (c.192C>A) in the AVP-NPII gene. The missense mutation resulted in the substitution of cysteine by serine at a highly conserved codon 65 of exon 2 of the AVP-NPII gene in all affected individuals, but not in unaffected members. We concluded that a novel missense mutation in the AVP-NPII gene caused neurohypophyseal diabetes insipidus in this family, due to impaired neurophysin function as a carrier protein for AVP. The Cys65 is essential for NPII in the formation of a salt bridge with AVP. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the normal expression of vasopressin.
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PMID:Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin-neurophysin II gene. 2230 87