Metabolism of signalling nucleotides

Parent categories	2. Metabolism 2.5. Nucleotide metabolism
Neighbouring categories	2.5.1. Utilization of nucleotides 2.5.2. Biosynthesis/ acquisition of nucleotides 2.5.3. Metabolism of signalling nucleotides 2.5.4. Nucleotide metabolism/ other
Related categories	DAC domain EAL domain GGDEF domain
Overview on the categories (Excel file) All genes and their categories (Excel file)

Genes in this functional category

ppGpp synthesis and degradation

• RelA
• SasA
• SasB

c-di-AMP synthesis

• DisA
• CdaA
• CdaS

Control of c-di-AMP synthesis

• CdaR controls CdaA activity PubMed
• RadA controls DisA activity PubMed

Note that c-di-AMP is essential for the growth of B. subtilis, but accumulation of the nucleotide is detrimental as well PubMed

c-di-AMP degradation

• GdpP
• PgpH

Protein potentially involved in c-di-GMP metabolism and signalling

Proteins containing a GGDEF domain (potential diguanylate cyclases)

• DgcK, has cyclase activity
• DgcW, has cyclase activity, contains both a GGDEF and an EAL domain
• DgcP, has cyclase activity
• YdaK, no activity, degenerate GGDEF domain
• GdpP, no diguanylate cyclase activity, is c-di-AMP specific phosphodiesterase (see above), degenerate GGDEF domain

Proteins containing an EAL domain (potential c-di-GMP phosphodiesterases)

• PdeH, has phosphodiesterase activity
• YkuI, no phosphodiesterase activity
• DgcW, phosphodiesterase activity not demonstrated, contains both a GGDEF and an EAL domain

Targets of signalling nucleotides

• ppGpp targets
  • DnaG
  • GdpP
  • Gmk
  • GuaB
  • HprT
  • RbgA
  • Era
  • YnbA

• c-di-GMP targets
  • DgrA (contains a PilZ domain)

• other c-di-GMP-binding proteins
  • YdaK
  • YkuI

• c-di-AMP targets
  • DarA PubMed
  • KtrC (binds c-di-AMP in vivo) PubMed
  • the ydaO riboswitch PubMed

Important reviews

Erin B Purcell, Rita Tamayo
Cyclic diguanylate signaling in Gram-positive bacteria.
FEMS Microbiol Rev: 2016, 40(5);753-73
[PubMed:27354347] [WorldCat.org] [DOI] (I p)

TuAnh Ngoc Huynh, Joshua J Woodward
Too much of a good thing: regulated depletion of c-di-AMP in the bacterial cytoplasm.
Curr Opin Microbiol: 2016, 30;22-29
[PubMed:26773214] [WorldCat.org] [DOI] (I p)

Fabian M Commichau, Achim Dickmanns, Jan Gundlach, Ralf Ficner, Jörg Stülke
A jack of all trades: the multiple roles of the unique essential second messenger cyclic di-AMP.
Mol Microbiol: 2015, 97(2);189-204
[PubMed:25869574] [WorldCat.org] [DOI] (I p)

Kuanqing Liu, Alycia N Bittner, Jue D Wang
Diversity in (p)ppGpp metabolism and effectors.
Curr Opin Microbiol: 2015, 24;72-9
[PubMed:25636134] [WorldCat.org] [DOI] (I p)

Rebecca M Corrigan, Angelika Gründling
Cyclic di-AMP: another second messenger enters the fray.
Nat Rev Microbiol: 2013, 11(8);513-24
[PubMed:23812326] [WorldCat.org] [DOI] (I p)

Dimpy Kalia, Gökçe Merey, Shizuka Nakayama, Yue Zheng, Jie Zhou, Yiling Luo, Min Guo, Benjamin T Roembke, Herman O Sintim
Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis.
Chem Soc Rev: 2013, 42(1);305-41
[PubMed:23023210] [WorldCat.org] [DOI] (I p)

Mark Gomelsky
cAMP, c-di-GMP, c-di-AMP and now cGMP: bacteria use them all!
Mol Microbiol: 2011, 79(3);562-5
[PubMed:21255104] [WorldCat.org] [DOI] (I p)

Tilman Schirmer, Urs Jenal
Structural and mechanistic determinants of c-di-GMP signalling.
Nat Rev Microbiol: 2009, 7(10);724-35
[PubMed:19756011] [WorldCat.org] [DOI] (I p)

Regine Hengge
Principles of c-di-GMP signalling in bacteria.
Nat Rev Microbiol: 2009, 7(4);263-73
[PubMed:19287449] [WorldCat.org] [DOI] (I p)

Ute Römling
Great times for small molecules: c-di-AMP, a second messenger candidate in Bacteria and Archaea.
Sci Signal: 2008, 1(33);pe39
[PubMed:18714086] [WorldCat.org] [DOI] (I e)

Peggy A Cotter, Scott Stibitz
c-di-GMP-mediated regulation of virulence and biofilm formation.
Curr Opin Microbiol: 2007, 10(1);17-23
[PubMed:17208514] [WorldCat.org] [DOI] (P p)

Ute Römling, Mark Gomelsky, Michael Y Galperin
C-di-GMP: the dawning of a novel bacterial signalling system.
Mol Microbiol: 2005, 57(3);629-39
[PubMed:16045609] [WorldCat.org] [DOI] (P p)