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PMID:19560421

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Citation

Wang, H, Piatkov, KI, Brower, CS and Varshavsky, A (2009) Glutamine-specific N-terminal amidase, a component of the N-end rule pathway. Mol. Cell 34:686-95

Abstract

Deamidation of N-terminal Gln by Nt(Q)-amidase, an N-terminal amidohydrolase, is a part of the N-end rule pathway of protein degradation. We detected the activity of Nt(Q)-amidase, termed Ntaq1, in mouse tissues, purified Ntaq1 from bovine brains, identified its gene, and began analyzing this enzyme. Ntaq1 is highly conserved among animals, plants, and some fungi, but its sequence is dissimilar to sequences of other amidases. An earlier mutant in the Drosophila Cg8253 gene that we show here to encode Nt(Q)-amidase has defective long-term memory. Other studies identified protein ligands of the uncharacterized human C8orf32 protein that we show here to be the Ntaq1 Nt(Q)-amidase. Remarkably, "high-throughput" studies have recently solved the crystal structure of C8orf32 (Ntaq1). Our site-directed mutagenesis of Ntaq1 and its crystal structure indicate that the active site and catalytic mechanism of Nt(Q)-amidase are similar to those of transglutaminases.

Links

PubMed PMC2749074 Online version:10.1016/j.molcel.2009.04.032

Keywords

Amidohydrolases/chemistry; Amidohydrolases/genetics; Amidohydrolases/isolation & purification; Amidohydrolases/physiology; Amino Acid Sequence; Animals; Binding Sites; Cattle; Cloning, Molecular; Conserved Sequence; Crystallography, X-Ray; Escherichia coli/genetics; Glutamine/chemistry; Glutamine/metabolism; Half-Life; Mice; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; NIH 3T3 Cells; Protein Structure, Tertiary; Saccharomyces cerevisiae/genetics; Substrate Specificity

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NTAQ1

involved_in

GO:0030163: protein catabolic process

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NTAQ1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NTAQ1

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NTAQ1

involved_in

GO:0006464: cellular protein modification process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NTAQ1

enables

GO:0070773: protein-N-terminal glutamine amidohydrolase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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