Cited by 80Sexual Differentiation and DisordersAdrenal Hormones and DisordersSteroid Chemistry and Biochemistry

Structural Analysis of the Gene Encoding Human 3β-Hydroxysteroid Dehydrogenase/δ5→4-lsomerase

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Lorence, Matthew C., Corbin, C. Jo, Kamimura, Naohisa, Mahendroo, Mala S., Mason, J. Ian·1990·Molecular Endocrinology

Abstract

The structural gene encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta HSD) was isolated from a human EMBL3 genomic library. The gene encompasses approximately 8 kilobases of DNA and is comprised of two large introns and three exons encoding amino acid residues 1-48, 49-103, and 104-373, respectively. The exonic sequence is identical to that of the cDNA that we previously isolated and expressed in COS 1 cells. DNA sequence analysis reveals a putative TATA (TATATAA) motif 26 basepairs up-stream of the beginning of exon I, as determined by S1 nuclease protection analysis. However, primer extension analysis using poly(A)+ RNA isolated from both placenta and corpora lutea indicates that the RNA initiates up-stream of the putative TATA motif, and that an additional 53-basepair exon, which is untranslated, is present 5' to the first coding exon. Southern hybridization analysis of genomic DNA using a single exon probe suggests that there may be more than one copy of the gene in the human genome. In addition, we confirm from Southern analysis of genomic DNA isolated from human x hamster somatic cell hybrids that the gene is located on human chromosome 1. These findings will provide a foundation for the characterization of apparent 3 beta HSD clinical deficiencies when these are due to a mutation in the structural gene.

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Authors
Lorence, M. C., Corbin, C. J., Kamimura, N., Mahendroo, M. S., & Mason, J. I.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • The University of Texas at Dallas (US)
Venue
Molecular Endocrinology
Published
1990-12
Volume
4
Issue
12
Pages
1850-1855
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
OpenAlex
W1991542972
Cited by
80
References
12
Citations by year
2023: 2 · 2018: 2 · 2016: 3 · 2015: 5 · 2013: 3 · 2012: 3
FWCI
1.71
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health (5r01ag008175-05, HD-11149)
  • Cecil H. and Ida Green Center for Reproductive Biology Sciences
  • National Institute on Aging (AG 08175)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-11149)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
Keywords
3β-hydroxysteroid dehydrogenase, gene structure, chromosome 1, TATA box, transcription initiation, introns and exons, gene copy number, placenta, corpus luteum, steroidogenesis, congenital adrenal hyperplasia
MeSH terms
Amino Acid Sequence, Base Sequence, Exons, Genes, Humans, Introns, Molecular Sequence Data, Multienzyme Complexes, Nucleic Acid Hybridization, Placenta, Progesterone Reductase, Steroid Isomerases, Restriction Mapping, Deoxyribonuclease EcoRI, DNA Probes, Polymerase Chain Reaction, TATA Box

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