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PMID: 1924293 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 19 ·1991-10-01 ·Pages 8337-41

Karlsen AE, Hagopian WA, Grubin CE, Dube S, Disteche CM, Adler DA, Bärmeier H, Mathewes S, Grant FJ, Foster D

Abstract

Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy-lyase, EC 4.1.1.15), 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, we 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 from 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 less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined.

Related Genes
GAD-2
MeSH Terms
Amino Acid Sequence Base Sequence Blotting, Northern Blotting, Southern Chromosome Mapping Chromosomes, Human, Pair 10 Cloning, Molecular Gene Expression Genes Glutamate Dehydrogenase/genetics Humans Islets of Langerhans/enzymology Molecular Sequence Data Protein Conformation RNA, Messenger/genetics Sequence Alignment
Chemicals
RNA, Messenger Glutamate Dehydrogenase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Karlsen A E
Department of Medicine, University of Washington, Seattle 98195.
Hagopian W A
Grubin C E
Dube S
Disteche C M
Adler D A
Bärmeier H
Mathewes S
Grant F J
Foster D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.19.8337
Published
1991-10-01
Pages
8337-41
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52503
Subset
IM
Grants
NIDDK NIH HHS · R01 DK026190 · United States
NIDDK NIH HHS · DK26190 · United States
NIDDK NIH HHS · DK33873 · United States
NCRR NIH HHS · RR00166 · United States
Databases
GENBANK
M64687, M64688, M74826, M94197, M94198, M94199, M94200, S55106, S57129, X53420
External Links
PubMed source DOI: 10.1073/pnas.88.19.8337 PMC Full Text View journal details
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