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Table 1 Classification of CNB domains in the public and GOS data

From: Evolution of allostery in the cyclic nucleotide binding module

No. Family name NR/GOS count Taxonomic origin PBC consensus motif Description
1 PKA-Rsub 301/0 Eukaryote GELALIYGTPRAATVVA cAMP dependent regulatory subunit that activates PKA
2 PKG 388/9 Eukaryote GELALLYNDPRTATVIA cGMP activated proteins that are typically attached to a kinase domain
3 PKG-parasites 362/11 Eukaryote GERALLYDEPRSATIKA A distinct group of PKGs in parasites that are also attached to kinase domains
4 Other_eukaryotic 940/201 Eukaryote GELALLYNAPRAATVVA CNB domains from metazoans and plants. These are attached to various functional domains such as PKs, PAS domains, PP2C like phosphatases and phospholipases
5 Epac 150/1 Eukaryote GQLALVNDAPRAATIVL cAMP-dependent guanine nucleotide exchange factors. Typically attached to an amino-terminal DEP domain and a carboxy-terminal RasGEF domain
6 PDZ-GEF 125/0 Eukaryote GVSPTMDKEYMKGVMRT A distinct class of Epac's, also called Epac6, which contains a PDZ domain in between the CNB and RasGEF domain. Epac's of this class contain a non-canonical PBC
7 K-channel 86/0 Eukaryote GEVGVLCYRPQLFTVRT Potassium channels specific to plants. Most of them contain an Ankryin repeat carboxy-terminal to the CNB domain
8 LR_CC 148/4 Eukaryote GEIGVLLDPPRTATVRA CNB domains found in metazoans and fungi, usually occur in tandem like the PKA regulatory subunit and contain a carboxy-terminal F-box domain and leucine rich domain
9 HCN 165/5 Eukaryote GEICLLTRGRRTASVRA cGMP-gated cation channels. Mostly present in metazoans
10 K_HCN 185/0 Eukaryote GENFWLYGTKSNADVRA Potassium channels that contain a PAC motif (motif carboxy-terminal of PAS) amino-terminal of the trans-membrane segment. This subfamily also contains a non-canonical PBC
11 Channel_Tetrahym. 218/44 Eukaryote GEEDFFSGQPRTFTAKC Likely HCN channels from the single celled eukaryote Tetrahymena thermophila. This subfamily is quite distinct from the HCN channels in higher eukaryotes
12 Channel_protozoa 587/41 Eukaryote GEISFFTGLPRTASARS Other HCN channels in protozoans
13 Bact_Pyrredox 38/70 Prokaryote GEMGLISGRRRGATVRA Tandem CNB domains that are attached to an amino-terminal pyridine nucleotide-disulphide oxidoreductase domain
14 Channel_Bact 99/79 Prokaryote GEIALLTGGPRTATVRA Bacterial CNBs that are attached to mechanosensitive ion channels
15 HisK 56/11 Prokaryote GELSLLTGGPRSATVRA Bacterial CNBs that contain a HisK like ATPase, carboxy-terminal of the CNB domain
16 AAA_Atpase 65/24 Prokaryote GEMALLSGQERKASVIA A distinct sub-group containing AAA-ATPase domains attached to the CNB domain. Several members of this group contain an ABC-transporter like transmembrane region. The PBC arginine (Arg209) is quite variable within this family
17 NtcA 108/104 Prokaryote GVLSLLTGSDRFYHAVA Nitrogen responsive regulatory protein that contains a DNA binding domain (HTH) carboxy-terminal of the CNB domain
18 FixK 43/0 Prokaryote G-ASLGGDHLFTAEA Involved in nitrogen fixation and contains a HTH motif
19 FnR 176/53 Prokaryote GEFDAIGSGHHPSFAQA Transcriptional regulators that are implicated in oxygen sensing
20 ArcR 29/0 Prokaryote PYGGLFTDDYYHESATA Transcriptional regulator that is implicated in the aerobic arginase reaction. Arginine is used as a source of energy in bacteria
21 NnR 28/0 Prokaryote GFARALQRGDYPGTATA Transcriptional regulators that act on the nir and nor operons to achieve expression under aerobic conditions
22 CBS 173/51 Prokaryote GERALLAGGPYSLTARA This group contains tandem CBS domain located carboxy-terminal of the CNB domain
23 Other_bacterial 1553/1486 Prokaryote GEMALLDGEPRSATVVA Bacterial CNB domains that are attached to various functional domains such as CheY response regulators, Rhodanese homology domain, kinases and DNA binding domains
24 HTH_ICLR 33/14 Prokaryote GEGAAFSEEPRSTTVVA Transcriptional regulator that is implicated in the repression of the acetate operon (also known as glyoxylate bypass operon) in Escherichia coli and Salmonella typhimurium
25 HTH_GNTR 85/52 Prokaryote GEASLFDGEPRSATVVA Transcriptional regulator containing a HTH domain and implicated in the repression of the gluconate operon
26 Flp 19/0 Prokaryote GEEALFGESNHANYCEA Involved in the bacterial oxidative stress response
27 HTH_ARSR 66/15 Prokaryote GEAALFSNGPYPATAIA Functions as a transcriptional repressor of an arsenic resistance operon. Dissociates from DNA in the presence of the metal
28 HTH_CRP 858/347 Prokaryote GEAALFDGGPRPATAVA Transcriptional regulation of the crp operon
29 HTH_MARR 143/20 Prokaryote GEMALLDGGPRSADAVA Repressor of genes that activate the multiple antibiotic resistance and oxidative stress regulons
30 HTH_ASNC 73/24 Prokaryote GEIALLDGGPRSATATA An autogenously regulated activator of asparagine synthetase A transcription in Escherichia coli