PROSITE documentation PDOC51707
CYTH domain profile


The CyaB like adenylyl cyclase and the mammalian thiamine triphosphatases (ThTPases) define a superfamily of catalytic domains called the CYTH (CyaB, thiamine triphosphatase) domain that is present in all three superkingdoms of life. CYTH domains are likely to be domains specialized to bind nucleotides and other organic phosphates [1].

The catalytic core of the CYTH domain is predicted to contain an α+β scaffold with 6 conserved β-strands and 6 conserved α-helices. The CYTH domains contains several nearly universally conserved charged residues that are likely to form the active site. The most prominent of these are an EXEXK motif associated with strand-1 of the domain, two basic residues in helix-2, a K at the end of strand 3, an E in strand 4, a basic residue in helix-4, a D at the end of strand 5 and two acidic residues (typically glutamates) in strand 6. The presence of around 6 conserved acidic positions in the majority of the CYTH domains suggests that it coordinates two divalent metal ions. Both CyaB and ThTPase have been shown to require Mg(2+) ions for their nucleotide cyclase and phosphatase activities. The four conserved basic residues in the CYTH domain are most probably involved in the binding of acidic phosphate moieties of their substrates. The conservation of these two sets of residues in the majority of CYTH domains suggests that most members of this group are likely to possess an activity dependent on two metal ions, with a preference for nucleotides or related phosphate-moiety -bearing substrates. The proposed biochemical activity, and the arrangement of predicted strands in the primary structure of the CYTH domain imply that they may adopt a barrel or sandwich-like configuration, with metal ions and the substrates bound in the central cavity [1].

The profile we developed covers the entire CYTH domain.

Last update:

February 2014 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

CYTH, PS51707; CYTH domain profile  (MATRIX)


1AuthorsIyer L.M. Aravind L.
TitleThe catalytic domains of thiamine triphosphatase and CyaB-like adenylyl cyclase define a novel superfamily of domains that bind organic phosphates.
SourceBMC Genomics 3:33-33(2002).
PubMed ID12456267

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