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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