Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10

Journal Article · Tue Oct 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.19.8337· OSTI ID:5703512

Karlsen, A E; Hagopian, W A; Grubin, C E; Dube, S; Disteche, C M; Adler, D A; Baermeier, H; Lernmark, A ^[1]; Mathewes, S; Grant, F J; Foster, D ^[2]

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1. Univ. of Washington, Seattle (United States)
2. Zymogenetics Inc., Seattle, WA (United States)

Glutamic acid decarboxylase which catalyzes formation of {gamma}-aminobutyric acid from L-glutamic acid, is detectable in different isoforms with distinct electrophoretic and kinetic characteristics. GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. Despite the differing GAD isoforms, only one type of GAD cDNA (GAD-1), localized to a syntenic region of chromosome 2, has been isolated from rat, mouse, and cat. Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, the authors describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different form that detected by GAD-1. GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. The deduced 585-amino acid sequence coded for by GAD-2 shows < 65% identify to previously published, highly conserved GAD-1 brain sequences, which show > 96% deduced amino acid sequence homology among the three species.

• OSTI ID: 5703512
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:19; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
DNA-CLONING
HETEROCHROMOSOMES
GENETIC MAPPING
RECOMBINANT DNA
DNA SEQUENCING
AMINO ACID SEQUENCE
BRAIN
CATS
DECARBOXYLASES
GLUTAMIC ACID
MAN
MICE
MOLECULAR STRUCTURE
PHOSPHORUS 32
RATS
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHROMOSOMES
CLONING
DAYS LIVING RADIOISOTOPES
DNA
DNA HYBRIDIZATION
ENZYMES
HYBRIDIZATION
ISOTOPES
LIGHT NUCLEI
LYASES
MAMMALS
MAPPING
NERVOUS SYSTEM
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550200* - Biochemistry