Bis(5'-nucleosyl)-tetraphosphatase (IPR003565)

Short name: Tetra_PHTase

Overlapping homologous superfamilies

Family relationships



Bis(5'-nucleosyl)-tetraphosphatase, also known as diadenosine tetraphosphate (Ap4A) hydrolase, is a member of the Nudix hydrolase superfamily. Ap4A hydrolases are well represented in a variety of prokaryotic and eukaryotic organisms [PMID: 16378245]. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one subfamily and fungi/animals/archaea enzymes, represented by this subfamily, fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for inhibition of such invasive bacteria [PMID: 14739989, PMID: 11007995, PMID: 16378245,PMID: 8810257, PMID: 16359314]. Besides the signature nudix motif (G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val) that functions as a metal binding and catalytic site, and a required divalent cation, Ap4A hydrolase is structurally similar to the other members of the nudix superfamily with some degree of variation. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies [PMID: 15581572].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0008796 bis(5'-nucleosyl)-tetraphosphatase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
  • cd03428 (Ap4A_hydrolase_human_like)