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PMID: 8643671 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 4 ·1996-02-20 ·Pages 1560-5

Karlin S, Burge C

Abstract

Several human neurological disorders are associated with proteins containing abnormally long runs of glutamine residues. Strikingly, most of these proteins contain two or more additional long runs of amino acids other than glutamine. We screened the current human, mouse, Drosophila, yeast, and Escherichia coli protein sequence data bases and identified all proteins containing multiple long homopeptides. This search found multiple long homopeptides in about 12% of Drosophila proteins but in only about 1.7% of human, mouse, and yeast proteins and none among E. coli proteins. Most of these sequences show other unusual sequence features, including multiple charge clusters and excessive counts of homopeptides of length > or = two amino acid residues. Intriguingly, a large majority of the identified Drosophila proteins are essential developmental proteins and, in particular, most play a role in central nervous system development. Almost half of the human and mouse proteins identified are homeotic homologs. The role of long homopeptides in fine-tuning protein conformation for multiple functional activities is discussed. The relative contributions of strand slippage and of dynamic mutation are also addressed. Several new experiments are proposed.

MeSH Terms

Amino Acid Sequence Animals Base Sequence Drosophila melanogaster/genetics Escherichia coli/genetics Genes Genes, Homeobox Homeodomain Proteins/chemistry,genetics Humans Mice/genetics Mice, Neurologic Mutants Molecular Sequence Data Multigene Family Nervous System/embryology,growth & development Nervous System Diseases/genetics Saccharomyces cerevisiae/genetics Species Specificity Transcription Factors/chemistry,genetics Trinucleotide Repeats

Chemicals

Homeodomain Proteins Transcription Factors

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Karlin S

Department of Mathematics, Stanford University, CA 94305-2125, USA.

Burge C

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19 references, click to expand

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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.93.4.1560

Published

1996-02-20

Pages

1560-5

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC39980

Subset

Grants

NIGMS NIH HHS · 2R01GM10452-31 · United States

NHGRI NIH HHS · 5R01HG00335-07 · United States

Databases

GENBANK

P04632, P07199, P10275, P10323, P10645, P11161, P14314, P14651, P14866, P17483, P18146, P19338, P20042, P20265, P20396, P22670, P23327, P23610, P25440, P25490, P32242, P35568, P41225, P42858, Q01851, Q03052, Q05925, Q06481, Q06945, S46268

External Links

PubMed source DOI: 10.1073/pnas.93.4.1560 PMC Full Text View journal details

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Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development.

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