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
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, modified GGDEF domain
• GdpP, no diguanylate cyclase activity, is c-di-AMP specific phosphodiesterase (see above), modified 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

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)