CaBP Data Library General Information

Calmodulin

Primary information about calmodulin:
Basic chemical and physical information
Basic biological information
Basic genomic information
Metal ion binding constants
Interspecies sequence alignment
Information on function
Summary of structural studies
Information on the conformational change List of available structures Information about mutations
References about calmodulin Other web resources about calmodulin
Additional information about calmodulin:
Two-dimensional "sequence map"
Information about the evolutionary relationship of calmodulin to other proteins
A summary of mutational studies on the Phe residues in yeast calmodulin
Links to contact maps of calmodulin Dihedral angles in apo and calcium-loaded calmodulin Per atom solvent accessible surface area in apo and calcium-loaded calmodulin

Basic Information

Additional names and abbreviations: calmodulin: calmodulin (CaM); modulator protein
Isoforms: isoform 1 (the main isoform, and the only isoform found in most species)
plant isoform 2 (isoform found only in some plants)
plant isoform 4 (isoform found only in some plants)
plant isoform 6 (isoform found only in some plants)
Yeast Protein Database Entries: CMD1


Basic Chemical and Physical Information:
Number of amino acids: isoform 1: 147 (Fagus sylvatica, Saccharomyces cerevisiae, Kluyveromyces lactis) - 162 (Chlamydomonas reinhardtii)
plant isoform 2: 148 (all species)
plant isoform 4: 148 (all species)
plant isoform 6: 148 (all species)
View a list of all sources stored in the database
Molecular weight: isoform 1: 16.063 kD (Kluyveromyces lactis) - 18.165 kD (Chlamydomonas reinhardtii)
plant isoform 2: 16.688 kD (Arabidopsis thaliana) - 16.806 kD (Petunia hybrida)
plant isoform 4: 16.704 kD (all species)
plant isoform 6: 16.702 kD (all species)
View a list of all sources stored in the database
pI: isoform 1: calculated pI (Homo sapiens) = 3.9 (InfoCard)
Number of functional calcium binding sites: isoform 1, vertebrates: 4 (InfoCard)
Macroscopic calcium binding constants: isoform 1, Bos taurus, low salt: K1 = 1 x 107; K2 = 3.98 x 107; K3 = 3.16 x 106; K4 = 2.5 x 106 (measured by: competitive chelator pH: 7.5 temperature: 25 degrees Celsius buffer: 0.002 M Tris-HCl ) (InfoCard)
isoform 1, Bos taurus, medium salt: K1 = 1.58 x 106; K2 = 2.5 x 107; K3 = 1 x 106; K4 = 1 x 106 (measured by: competitive chelator pH: 7.5 temperature: 25 degrees Celsius salt: 10 mM KCl buffer: 0.002 M Tris-HCl ) (InfoCard)
isoform 1, Bos taurus, medium salt: K1 = 6.30 x 105; K2 = 1 x 107; K3 = 2.50 x 105; K4 = 5.00 x 105 (measured by: competitive chelator pH: 7.5 temperature: 25 degrees Celsius salt: 25 mM KCl buffer: 0.002 M Tris-HCl ) (InfoCard)
isoform 1, Bos taurus, medium salt: K1 = 2.50 x 105; K2 = 5 x 106; K3 = 3.98 x 104; K4 = 3.16 x 105 (measured by: competitive chelator pH: 7.5 temperature: 25 degrees Celsius salt: 50 mM KCl buffer: 0.002 M Tris-HCl ) (InfoCard)
isoform 1, Bos taurus, medium salt: K1 = 7.90 x 104; K2 = 3.98 x 106; K3 = 2.50 x 104; K4 = 3.98 x 105 (measured by: competitive chelator pH: 7.5 temperature: 25 degrees Celsius salt: 100 mM KCl buffer: 0.002 M Tris-HCl ) (InfoCard)
isoform 1, Bos taurus, high salt: K1 = 5.00 x 104; K2 = 1.58 x 106; K3 = 1.00 x 104; K4 = 2.00 x 105 (measured by: competitive chelator pH: 7.5 temperature: 25 degrees Celsius salt: 150 mM KCl buffer: 0.002 M Tris-HCl ) (InfoCard)
Other metal binding constants: not yet available in the data library
Protein stability: not yet available in the data library
Post-translational modifications: isoform 1, flowering plants: trimethylation at Lys115 (InfoCard)
isoform 1, mammals: phosphorylation (made by: casein kinase II effect: Alters the ability of calmodulin to activate selected target enzymes. No apprent effect on calicium binding to calmodulin. ) (InfoCard)
isoform 1, mammals: phosphorylation (made by: insulin receptor kinase effect: Alters the ability of calmodulin to activate selected target enzymes. No apprent effect on calicium binding to calmodulin. ) (InfoCard)
isoform 1, vertebrates: trimethylation at Lys115 (InfoCard)
isoform 1, Rattus norvegicus: phosphorylation (made by: insulin receptor kinase) (InfoCard)


Basic Biological Information:
Source organisms: isoform 1: eukaryotes
plant isoform 2: Arabidopsis thaliana, Petunia hybrida
plant isoform 4: Arabidopsis thaliana
plant isoform 6: Arabidopsis thaliana
View an annotated list of all sources stored in the database
Tissues: isoform 1, eukaryotes: all tissues and cells (InfoCard)
Subcellular localization: not yet available in the data library
Regulation: not yet available in the data library


Genomic Information:
GenBank entries: View a list of GenBank entries stored in the database
Gene length: not yet available in the data library
Gene structure: not yet available in the data library
Promoter: not yet available in the data library
Gene copies: isoform 1, Homo sapiens: 3 gene copies (code for an indentical protein) (InfoCard)
Alleles: no alleles are currently stored in the data library
Chromosomal localization: isoform 1, Homo sapiens, expressed (GenBank code U12022): q24-q31 region of chromosome 14 (CALM1) (InfoCard)
isoform 1, Homo sapiens, expressed (GenBank code U94728): p21.1-21.3 region of chromosome 2 (CALM2) (InfoCard)
isoform 1, Homo sapiens, expressed (GenBank code X52606): q13.2-13.3 region of chromosome 19 (CALM3) (InfoCard)

Interspecies Sequence Alignment




                     |-helixI-|--loop1----|helixII|
                      En**nn**nX*Y*ZG#Ix**zn**nn*n

HUMAN   :   ADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAEL
SPOMBE  : MTTRNLTDEQIAEFREAFSLFDRDQDGNITSNELGVVMRSLGQSPTAAEL
SCEREV  :  MSSNLTEEQIAEFKEAFALFDKDNNGSISSSELATVMRSLGLSPSEAEV


         |helixIII|--loop2----|helixIV|        |-helixV-|-loop3
          En**nn**nX*Y*ZG#Ix**zn**nn*n         En**nn**nX*Y*ZG

HUMAN   : ELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNG
SPOMBE  : ELQDMINEVDADGNGTIDFTEFLTMMARKMKDTDNEEEVREAFKVFDKDGNG
SCEREV  : EVNDLMNEIDVDGNHQIEFSEFLALMSRQLKSNDSEQELLEAFKVFDKNGDG

          -----|helixVI|      |helixVII|--loop4----|helixVIII|
          #Ix**zn**nn*n        En**nn**nX*Y*ZG#Ix**zn**nn*n

HUMAN   : YISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK
SPOMBE  : YITVEELTHVLTSLGERLSQEEVADMIREADTDGDGVINYEEFSRVISSK
SCEREV  : LISAAELKHVLTSIGEKLTDAEVDDMLREVSDGSGEI-NIQQFAALLSK 


Loop 4 of SCEREV calmodulin does not bind calcium

Sequence alignment for the entire calmodulin subfamily

Functional Information:

General information:

Biological roles:

Disease states:

Target molecules:


Structural Information:

Calcium-coordination:
isoform 1, all vertebrates:
  • EF1 ; X = D20 OD2; Y = D22 OD1; Z = D24 OD2; -X = H2O; -Y = T26 O; -Z1 = E31 OE1; -Z2 = E31 OE2
  • EF2 ; X = D56 OD2; Y = D58 OD2; Z = N60 OD1; -X = H2O; -Y = T62 O; -Z1 = E67 OE1; -Z2 = E67 OE2
  • EF3 ; X = D93 OD2; Y = D95 OD2; Z = D97 OD1; -X = H2O; -Y = Y99 O; -Z1 = E104 OE1; -Z2 = E104 OE2
  • EF4 ; X = D129 OD1; Y = D131 OD2; Z = D133 OD2; -X = H2O; -Y = Q135 O; -Z1 = E140 OE1; -Z2 = E140 OE2 (InfoCard)


Nature of the conformational changes:
Conformational change between apo and four calcium ions bound states of isoform 1:
The conformational change is a reorganization of existing secondary structural elements in each domain.
Upon calcium-binding, the bottoms of helices I and II swing apart, while the tops pinch together; a similar change is observed for helices III and IV. The interface between helcies II and IV is completely disrupted, as the two helices move apart along their entire lengths. The interfaces beteen helices I and IV and between helices II and III are not much affected by calcium-binding.
(InfoCard)
Conformational change between four calcium ions bound and four calcium ions and target peptide bound states of isoform 1:
Target peptide binding to calcium-loaded calmodulin effects mainly the quarternary structure: the structure of the two domains is not changed.
In the absence of peptide, the two domains do not interact to a large extent, and the linekr between the two domains is flexible. Peptide binding causes calmodulin to compact, as the two domains wrap around the target peptide, with CaM-C interacting with the N-terminal portion of one face of the peptide and CaM-N interacting with the C-terminal portion of the other face.
The flexible nature of the tether between the two domains allows calmodulin to bind to peptides of varying length.
(InfoCard)


Secondary structure:
(as reported in the PDB file and its accompanying reference)
isoform 1, all vertebrates, four calcium ions bound state:
Helices:
N-terminal domain: helix 1: 5 - 19, helix 2: 29 - 37, helix 3: 45 - 55, helix 4: 65 - 75,
C-terminal domain: helix 5: 82 - 92, helix 6: 102 - 111, helix 7: 118 - 128, helix 8: 138 - 146
Beta strands:
N-terminal domain: strand 1: 27 - 29, strand 2: 63 - 65,
C-terminal domain: strand 3: 100 - 102, strand 4: 136 - 138
(pdb code 1CLL: InfoCard)
isoform 1, all vertebrates, apo state:
Helices:
N-terminal domain: helix 1: 6 - 19, helix 2: 29 - 38, helix 3: 45 - 55, helix 4: 65 - 75,
C-terminal domain: helix 5: 82 - 91, helix 6: 102 - 111, helix 7: 118 - 127, helix 8: 139 - 146
Beta strands:
N-terminal domain: strand 1: 26 - 28, strand 2: 62 - 64
(pdb code 1CFC: InfoCard)


Additional structural information:


Available structures:
(follow the links from the PDB code to the retrieve the
PDB files)
Apo Structures:
1CMF: isoform 1, Bos taurus, C-terminal domain, pH 6
NMR solution structure, 20 models
(InfoCard)
1CFC: isoform 1, Xenopus laevis, full length protein, pH 6.3
NMR solution structure, 25 models, 27.7 restraints per residue
(InfoCard)
1DMO: isoform 1, Xenopus laevis, full length protein, pH 7.5
NMR solution structure, 30 models, 18.02 restraints per residue
(InfoCard)
Calcium Loaded Structures:
1CMG: isoform 1, Bos taurus, C-terminal domain, pH 6
NMR solution structure, 20 models
2 Ca ions bound
(InfoCard)
1TRC: isoform 1, Bos taurus, C-terminal domain,
Crystal structure, 3.6 angstrom resolution, R-value = 25.7
2 Ca ions bound
(InfoCard)
1OSA: isoform 1, Paramecium tetraurelia, full length protein,
Crystal structure, 1.68 angstrom resolution, R-value = 19.4
4 Ca ions bound
(InfoCard)
1CLM: isoform 1, Paramecium tetraurelia, full length protein,
Crystal structure, 1.8 angstrom resolution, R-value = 21
4 Ca ions bound
(InfoCard)
4CLN: isoform 1, Drosophila melanogaster, full length protein,
Crystal structure, 2.2 angstrom resolution, R-value = 19.7
4 Ca ions bound
(InfoCard)
1CLL: isoform 1, Homo sapiens, full length protein, pH 5
Crystal structure, 1.7 angstrom resolution, R-value = 21.6
4 Ca ions bound
(InfoCard)
3CLN: isoform 1, Rattus norvegicus, full length protein, pH 5.6
Crystal structure, 2.2 angstrom resolution, R-value = 17.5
4 Ca ions bound
(InfoCard)
Other Metal Bound Structures:
1AK8: isoform 1, Bos taurus, N-terminal domain,
NMR solution structure, 23 models, 13.15 restraints per residue
2 Ce ions bound
(InfoCard)
Target Peptide Bound Structures:
2BBN: isoform 1, Drosophila melanogaster, full length protein, pH 6.8
NMR solution structure, 24 models, 10.82 restraints per residue
4 Ca ions bound , bound to 1 equivalentsof the following portion of skeletal muscle myosin light chain kinase: peptide derived from the calmodulin binding domain of the skeletal muscle myosin light chain kinase
(InfoCard)
1CDL: isoform 1, Bos taurus, full length protein, pH 4.6
Crystal structure, 2.4 angstrom resolution, R-value = 22
4 Ca ions bound , bound to 1 equivalentsof the following portion of smooth muscle myosin light chain kinase: peptide derived from the calmodulin binding domain of the smooth muscle myosin light chain kinase
(InfoCard)
1CDM: isoform 1, Bos taurus, full length protein,
Crystal structure, 2 angstrom resolution, R-value = 20.8
4 Ca ions bound , bound to 1 equivalentsof the following portion of calcium/calmodulin-dependent protein kinase II: peptide derived from the calmodulin binding domain
(InfoCard)
Drug Bound Structures:
1CTR: isoform 1, Bos taurus, full length protein, pH 5.8
Crystal structure, 2.45 angstrom resolution, R-value = 22.2
4 Ca ions bound , bound to 1 equivalentsof the following portion of trifluoperazine: complete molecule
(InfoCard)
1LIN: isoform 1, Bos taurus, full length protein, pH 5.5
Crystal structure, 2 angstrom resolution, R-value = 22
4 Ca ions bound , bound to 4 equivalentsof the following portion of trifluoperazine: complete molecule
(InfoCard)
1A29: isoform 1, Bos taurus, full length protein, pH 5.6
Crystal structure, 2.74 angstrom resolution, R-value = 19.7, R-free = 26.5
4 Ca ions bound , bound to 2 equivalentsof the following portion of trifluoperazine: complete molecule
(InfoCard)
Mutant Structures:
1AHR: isoform 1, Gallus gallus, full length protein, pH 4.25
Crystal structure, 1.8 angstrom resolution, R-value = 21.1
4 Ca ions bound
Mutations: T79 deleted + D80 deleted
(InfoCard)

Information about mutants: