SMART: cNMP domain annotation

cNMP Cyclic nucleotide-monophosphate binding domain

SMART accession number:	SM00100
Description:	Catabolite gene activator protein (CAP) is a prokaryotic homologue of eukaryotic cNMP-binding domains, present in ion channels, and cNMP-dependent kinases.
Interpro abstract (IPR000595):	Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues [(PUBMED:14638413), (PUBMED:10550204), (PUBMED:1710853)]. The best studied of these proteins is the prokaryotic catabolite gene activator (also known as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure. There are six invariant amino acids in this domain, three of which are glycine residues that are thought to be essential for maintenance of the structural integrity of the beta-barrel. cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. The cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain. The cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section. Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. Two such cations channels have been fully characterised, one is found in rod cells where it plays a role in visual signal transduction.
Family alignment:	View or

There are 12325 cNMP domains in 10887 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a cNMP domain in a specific node, click on it.

This tree shows only several representative species. The complete taxonomic breakdown of all proteins with cNMP domain is also avaliable.

Useful shortcuts: Expand all nodes or Collapse tree
Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Cellular role (predicted cellular role)
Binding / catalysis: cAMP-binding, cGMP-binding
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Shabb JB, Poteet CE, Kapphahn MA, Muhonen WM, Baker NE, Corbin JD
- Characterization of the isolated cAMP-binding B domain of cAMP-dependent protein kinase.
- Protein Sci. 1995; 4: 2100-6
- Display abstract
- A 14.4-kDa cAMP-binding fragment was generated during bacterial expression and purification of recombinant bovine cAMP-dependent protein kinase type I alpha regulatory subunit (RI alpha). The full-length RI alpha from which the fragment was derived contained a point mutation allowing its B domain to bind both cAMP and cGMP with high affinity while leaving its A domain highly cAMP selective. The NH2 terminus of the fragment was Ser-252, indicating that it encompassed the entire predicted B domain. Although the [3H]cAMP and [3H]cGMP exchange rates of the isolated B domain were increased relative to the B domain in intact RI alpha, the [3H]cAMP exchange rate was comparable to that of the B domain of full-length RI alpha containing an unoccupied A domain. A plasmid encoding only the isolated B domain was overexpressed in Escherichia coli, and a monomeric form of the B domain was purified that had identical properties to the proteolytically generated fragment, indicating that all of the elements for the high-affinity cAMP-binding B domain are contained within the 128 amino acid carboxyl terminus of the R subunit. Prolonged induction of the B domain in E. coli or storage of the purified protein resulted in the formation of a dimer that could be reverted to the monomer by incubation in 2-mercaptoethanol. Dimerization caused an approximate fivefold increase in the rate of cyclic nucleotide exchange relative to the monomer. The results show that an isolated cAMP-binding domain can function independently of any other domain structures of the R subunit.
- Schultz SC, Shields GC, Steitz TA
- Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees.
- Science. 1991; 253: 1001-7
- Display abstract
- The 3 angstrom resolution crystal structure of the Escherichia coli catabolite gene activator protein (CAP) complexed with a 30-base pair DNA sequence shows that the DNA is bent by 90 degrees. This bend results almost entirely from two 40 degrees kinks that occur between TG/CA base pairs at positions 5 and 6 on each side of the dyad axis of the complex. DNA sequence discrimination by CAP derives both from sequence-dependent distortion of the DNA helix and from direct hydrogen-bonding interactions between three protein side chains and the exposed edges of three base pairs in the major groove of the DNA. The structure of this transcription factor--DNA complex provides insights into possible mechanisms of transcription activation.
- Weber IT, Steitz TA, Bubis J, Taylor SS
- Predicted structures of cAMP binding domains of type I and II regulatory subunits of cAMP-dependent protein kinase.
- Biochemistry. 1987; 26: 343-51
- Display abstract
- The mammalian cAMP-dependent protein kinases have regulatory (R) subunits that show substantial homology in amino acid sequence with the catabolite gene activator protein (CAP), a cAMP-dependent gene regulatory protein from Escherichia coli. Each R subunit has two in-tandem cAMP binding domains, and the structure of each of these domains has been modeled by analogy with the crystal structure of CAP. Both the type I and II regulatory subunits have been considered, so that four cAMP binding domains have been modeled. The binding of cAMP in general is analogous in all the structures and has been correlated with previous results based on photolabeling and binding of cAMP analogues. The model predicts that the first cAMP binding domain correlates with the previously defined fast dissociation site, which preferentially binds N6-substituted analogues of cAMP. The second domain corresponds to the slow dissociation site, which has a preference for C8-substituted analogues. The model also is consistent with cAMP binding in the syn conformation in both sites. Finally, this model has targeted specific regions that are likely to be involved in interdomain contacts. This includes contacts between the two cAMP binding domains as well as contacts with the amino-terminal region of the R subunit and with the catalytic subunit.
- McKay DB, Steitz TA
- Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA.
- Nature. 1981; 290: 744-9
- Display abstract
- The 2.9 A resolution crystal structure of Escherichia coli catabolite gene activator protein (CAP) complexed with cyclic AMP reveals two distinct structural domains separated by a cleft. The smaller carboxy-terminal domain is presumed to bind DNA while the amino-terminal domain is seen to bind cyclic AMP. Model building studies suggest that CAP binds to left-handed B-type DNA, contracting its major groove via two alpha-helices. It is possible that the CAP conversion of right- to left-handed DNA in a closed supercoil, is what activates transcription by RNA polymerase.
- McKay DB, Fried MG
- Crystallization and preliminary X-ray diffraction data for the cyclic AMP receptor protein of Escherichia coli.
- J Mol Biol. 1980; 139: 95-6
Disease (disease genes where sequence variants are found in this domain)

Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Protein	Disease
Cyclic nucleotide-gated cation channel alpha-3 (Q16281) (SMART)	OMIM:216900: Achromatopsia OMIM:600053: Achromatopsia-2 OMIM:216900:
Potassium voltage-gated channel subfamily H member 2 (Q12809) (SMART)	OMIM:152427: Long QT syndrome-2

3D Structures of cNMP domains in PDB

PDB code	Main view	Title
1cgp		Catabolite gene activator protein (cap)/dna complex + adenosine-3',5'-cyclic-monophosphate
1cx4		Crystal structure of a deletion mutant of the type ii beta regulatory subunit of camp-dependent protein kinase
1ft9		Structure of the reduced (feii) co-sensing protein from r. rubrum
1g6n		2.1 angstrom structure of cap-camp
1hw5		The cap/crp variant t127l/s128a
1i5z		Structure of crp-camp at 1.9 a
1i6x		Structure of a star mutant crp-camp at 2.2 a
1j59		Catabolite gene activator protein (cap)/dna complex + adenosine-3',5'-cyclic-monophosphate
1lb2		Structure of the e. coli alpha c-terminal domain of rna polymerase in complex with cap and dna
1ne4		Crystal structure of rp-camp binding r1a subunit of camp- dependent protein kinase
1ne6		Crystal structure of sp-camp binding r1a subunit of camp- dependent protein kinase
1o3q		Protein-dna recognition and dna deformation revealed in crystal structures of cap-dna complexes
1o3r		Protein-dna recognition and dna deformation revealed in crystal structures of cap-dna complexes
1o3s		Protein-dna recognition and dna deformation revealed in crystal structures of cap-dna complexes
1o3t		Protein-dna recognition and dna deformation revealed in crystal structures of cap-dna complexes
1o5l		Crystal structure of transcriptional regulator (tm1171) from thermotoga maritima at 2.30 a resolution
1o7f		Crystal structure of the regulatory domain of epac2
1q3e		Hcn2j 443-645 in the presence of cgmp
1q43		Hcn2i 443-640 in the presence of camp, selenomethionine derivative
1q5o		Hcn2j 443-645 in the presence of camp, selenomethionine derivative
1rgs		Regulatory subunit of camp dependent protein kinase
1rl3		Crystal structure of camp-free r1a subunit of pka
1run		Catabolite gene activator protein (cap)/dna complex + adenosine-3',5'-cyclic-monophosphate
1ruo		Catabolite gene activator protein (cap) mutant/dna complex + adenosine-3',5'-cyclic-monophosphate
1u12		M. loti cyclic nucleotide binding domain mutant
1vp6		M.loti ion channel cylic nucleotide binding domain
1wgp		Solution structure of the cnmp-binding domain from arabidopsis thaliana cyclic nucleotide-regulated ion channel
1zrc		Crystal structures of cap-dna with all base-pair substitutions at position 6, cap-icap38 dna
1zrd		Crystal structures of cap-dna with all base-pair substitutions at position 6, cap-[6a;17t]icap38 dna
1zre		Crystal structures of cap-dna with all base-pair substitutions at position 6, cap-[6g;17c]icap38 dna
1zrf		Crystal structures of cap-dna with all base-pair substitutions at position 6, cap-[6c;17g]icap38 dna
1zyb		Crystal structure of transcription regulator from bacteroides thetaiotaomicron vpi-5482 at 2.15 a resolution
2byv		Structure of the camp responsive exchange factor epac2 in its auto-inhibited state
2cgp		Catabolite gene activator protein/dna complex, adenosine-3', 5'-cyclic-monophosphate
2d93		Solution structure of the cnmp_binding domain of human rap guanine nucleotide exchange factor 6
2fmy		Co-dependent transcription factor cooa from carboxydothermus hydrogenoformans (imidazole-bound form)
2gau		Crystal structure of transcriptional regulator, crp/fnr family from porphyromonas gingivalis (apc80792), structural genomics, mcsg
2gzw		Crystal structure of the e.coli crp-camp complex
2h6b		Crystal structure of oxidized cprk in complex with o- chlorophenolacetic acid
2h6c		Crystal structure of reduced cprk in absence of any ligand
2hkx		Structure of cooa mutant (n127l/s128l) from carboxydothermus hydrogenoformans
2k0g		Solution structure of a bacterial cyclic nucleotide- activated k+ channel binding domain in complex with camp
2oz6		Crystal structure of virulence factor regulator from pseudomonas aeruginosa in complex with camp
2pqq		Structural genomics, the crystal structure of the n- terminal domain of a transcriptional regulator from streptomyces coelicolor a3(2)
2ptm		Structure and rearrangements in the carboxy-terminal region of spih channels
2q0a		Structure and rearrangements in the carboxy-terminal region of spih channels
2qcs		A complex structure between the catalytic and regulatory subunit of protein kinase a that represents the inhibited state
2qvs		Crystal structure of type iia holoenzyme of camp-dependent protein kinase
2wc2		Nmr structure of catabolite activator protein in the unliganded state
2z69		Crystal structure of the sensor domain of the transcriptional regulator dnr from pseudomonas aeruginosa
2zcw		Crystal structure of ttha1359, a transcriptional regulator, crp/fnr family from thermus thermophilus hb8
2zd9		Structure of a bacterial cyclic-nucleotide regulated ion channel
2zdb		Crystal structure of tthb099, a transcriptional regulator crp family from thermus thermophilus hb8
3beh		Structure of a bacterial cyclic nucleotide regulated ion channel
3bpz		Hcn2-i 443-460 e502k in the presence of camp
3cf6		Structure of epac2 in complex with cyclic-amp and rap
3cl1		M. loti cyclic-nucleotide binding domain, cyclic-gmp bound
3clp		M. loti cyclic-nucleotide binding domain mutant 2
3co2		Mlotik1 ion channel cyclic-nucleotide binding domain mutant
3d0s		Camp receptor protein from m.tuberculosis, camp-free form
3dkw		Crystal structure of dnr from pseudomonas aeruginosa.
3dn7		Cyclic nucleotide binding regulatory protein from cytophaga hutchinsonii.
3dv8		Crystal structure of transcriptional regulator, crp/fnr family (rer070207001219) from eubacterium rectale at 2.55 a resolution
3e5q		Unbound oxidised cprk
3e5u		Ocpa complexed cprk (c200s)
3e5x		Ocpa complexed cprk
3e6b		Ocpa complexed cprk (c200s)
3e6c		Cprk ocpa dna complex
3e6d		Crystal structure of cprk c200s
3e97		Crystal structure of transcriptional regulator of crp/fnr family (yp_604437.1) from deinococcus geothermalis dsm at 1.86 a resolution
3etq		X-ray structure of cysteine-free fragment of mhcn2 c- terminal region from amino acids 443-630 including c508n, c584s, and c601s mutations
3ffq		Hcn2i 443-640 apo-state
3fhi		Crystal structure of a complex between the catalytic and regulatory (ri{alpha}) subunits of pka
3fwe		Crystal structure of the apo d138l cap mutant
3fx3		Structure of a putative camp-binding regulatory protein from silicibacter pomeroyi dss-3
3gyd		Crystal structure of cyclic nucleotide-binding domain (yp_546034.1) from methylobacillus flagellatus kt at 1.79 a resolution
3h3z		Crystal structure of putative camp-binding regulatory protein (yp_165150.1) from silicibacter pomeroyi dss-3 at 2.35 a resolution
3hif		The crystal structure of apo wild type cap at 3.6 a resolution.
3i54		Crystal structure of mtbcrp in complex with camp
3i59		Crystal structure of mtbcrp in complex with n6-camp
3idb		Crystal structure of (108-268)riib:c holoenzyme of camp- dependent protein kinase
3idc		Crystal structure of (102-265)riib:c holoenzyme of camp- dependent protein kinase
3iyd		Three-dimensional em structure of an intact activator- dependent transcription initiation complex
3kcc		Crystal structure of d138l mutant of catabolite gene activator protein

Links (links to other resources describing this domain)
BLOCKS CNMP_BINDING_1
PFAM cNMP_binding
INTERPRO IPR000595