Home Page for Troponin C

Troponin C

Primary information about troponin C:
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 troponin C	Other web resources about troponin C
Additional information about troponin C:
Information about the evolutionary relationship of troponin C to other proteins	Links to contact maps of troponin C	Dihedral angles in troponin C	Per atom solvent accessible surface area in troponin C

Basic Information

Basic Chemical and Physical Information:
Additional names and abbreviations:	No additional names are stored in the database
Isoforms:	cardiac isoform lower animal isoform 1 lower animal isoform 2 lower animal isoform 2A lower animal isoform 2B lower animal isoform 73F skeletal isoform
Yeast Protein Database Entries:	No links to the YPD are stored in the database

Number of amino acids:	cardiac isoform: 161 (all species) lower animal isoform 1: 150 (Pontastacus leptodactylus, Homarus americanus) - 158 (Balanus nubilis) lower animal isoform 2: 150 (Pontastacus leptodactylus) - 155 (Drosophila melanogaster) lower animal isoform 2A: 150 (all species) lower animal isoform 2B: 150 (all species) lower animal isoform 73F: 155 (all species) skeletal isoform: 52 (Protopterus dolloi) - 162 (Gallus gallus, Meleagris gallopavo, Rana esculenta) 152 (Patinopecten yessoensis) - 163 (Branchiostoma lanceolatum) View a list of all sources stored in the database
Molecular weight:	cardiac isoform: 18.402 kD (Oryctolagus cuniculus) - 18.43 kD (Gallus gallus) lower animal isoform 1: 16.996 kD (Homarus americanus) - 17.942 kD (Balanus nubilis) lower animal isoform 2: 16.796 kD (Balanus nubilis) - 17.895 kD (Drosophila melanogaster) lower animal isoform 2A: 17.038 kD (all species) lower animal isoform 2B: 16.951 kD (all species) lower animal isoform 73F: 17.611 kD (all species) skeletal isoform: 5.949 kD (Protopterus dolloi) - 18.284 kD (Meleagris gallopavo) 17.41 kD (Patinopecten yessoensis) - 19.041 kD (Branchiostoma lanceolatum) View a list of all sources stored in the database
pI:	not yet available in the data library
Number of functional calcium binding sites:	not yet available in the data library
Macroscopic calcium binding constants:	not yet available in the data library
Other metal binding constants:	not yet available in the data library
Protein stability:	not yet available in the data library
Post-translational modifications:	not yet available in the data library

Basic Biological Information:
Source organisms:	cardiac isoform: Gallus gallus, Homo sapiens, Mus musculus, Coturnix coturnix japonica, Oryctolagus cuniculus lower animal isoform 1: Balanus nubilis, Pontastacus leptodactylus, Drosophila melanogaster, Homarus americanus lower animal isoform 2: Balanus nubilis, Pontastacus leptodactylus, Drosophila melanogaster lower animal isoform 2A: Homarus americanus lower animal isoform 2B: Homarus americanus lower animal isoform 73F: Drosophila melanogaster skeletal isoform: Gallus gallus, Homo sapiens, Protopterus dolloi, Mus musculus, Sus scrofa, Oryctolagus cuniculus, Rana esculenta, Meleagris gallopavo Branchiostoma lanceolatum, Halocynthia roretzi, Tachypleus tridentatus, Patinopecten yessoensis View an annotated list of all sources stored in the database
Tissues:	not yet available in the data library
Subcellular localization:	not yet available in the data library
Regulation:	not yet available in the data library

Genomic Information:
GenBank entries:	not yet available in the data library
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:	not yet available in the data library
Alleles:	no alleles are currently stored in the data library
Chromosomal localization:	not yet available in the data library

Interspecies Sequence Alignment



                              |-helixA|--loop1-----|helixB|
                              En**nn**nX*Y*ZG#Ix**zn**nn*n

skeletal isoform::

CHICK   : ASMTDQQAEARAFLSEEMIAEFKAAFDMFDADGGGDISTKELGTVMRMLGQNPT
TURKEY  : PSMTDQQAEARAFLSEEMIAEFKAAFDMFDADGGGDISTKELGTVMRMLGQNPT
HUMAN   :    TDQQAEARSYLSEEMIAEFKAAFDMFDADGGGDISVKELGTVMRMLGQNPT
MOUSE   :    TDQQAEARSYLSEEMIAEFKAAFDMFDADGGGDISVKELGTVMRMLGQNPT
PORCINE :    DTQQAEARSYLSEEMIAEFKAAFDMFDADGGGDISVKELGTVMRMLGQNPT
RABBIT  :    TDQQAEARSYLSEEMIAEFKAAFDMFDADGGGDISVKELGTVMRMLGQNPT
RANES   : AQPTDQQMDARSFLSEEMIAEFKAAFDMFDTDGGGDISTKELGTVMRMLGQNPT

          |-helixC-|--loop2----|helixD|           |-helixE|
           En**nn**nX*Y*ZG#Ix**zn**nn*n            En**nn**

skeletal isoform::

CHICK   : KEELDAIIEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELANCFRI
TURKEY  : KEELDAIIEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELANCFRI
HUMAN   : KEELDAIIEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRI
MOUSE   : KEELDAIIEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRI
PORCINE : KEELDAIIEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRI
RABBIT  : KEELDAIIEEVDEDGSGTIDFEEFLVMMVRQMKEDAKGKSEEELAECFRI
RANES   : KEELDAIIEEVDEDGSGTIDFEEFLVMMVRQMKEDAQGKSEEELAECFRI

         |--loop3----|helixF|       |-helixG-|--loop4----|helixH|
         nX*Y*ZG#Ix**zn**nn*n        En**nn**nX*Y*ZG#Ix**zn**nn*n

skeletal isoform::

CHICK   : FDKNADGFIDIEELGEILRATGEHVTEEDIEDLMKDSDKNNDGRIDFDEFLKMMEGVQ 
TURKEY  : FDKNADGFIDIEELGEILRATGEHVTEEEIEDLMKDSDKNNDGRIDFDEFLKMMEGVQ
HUMAN   : FDRNADGYIDPEELAEIFRASGEHVTDEEIESLMKDGDKNNDGRIDFDEFLKMMEGVQ 
MOUSE   : FDRNADGYIDAEELAEIFRASGEHVTEEEIESLMKDGDKNNDGRIDFDEFLKMMEGVQ
PORCINE : FDRNMDGYIDAEELAEIFRASGEHVTDEEIESIMKDGDKNNDGRIDFDEFLKMMEGVQ 
RABBIT  : FDRNADGYIDAEELAEIFRASGEHVTDEEIESLMKDGDKNNDGRIDFDEFLKMMEGVQ 
RANES   : FDKNADGYIDSEELGEILRSSGESITDEEIEELMKDGDKNNDGKIDFDEFLKMMEGVQ

Sequence alignment of the entire calmodulin subfamily

Functional Information:

General information:

cardiac isoform, in Gallus gallusNeither the skeletal nor cardiac isoform of troponin C can effectively activate most calmodulin targets (InfoCard)
skeletal isoform, in Gallus gallusNeither the skeletal nor cardiac isoform of troponin C can effectively activate most calmodulin targets (InfoCard)
skeletal isoform, in Gallus gallusCalmodulin does not successfully substitute for troponin C in skinned skeletal muscle fibers (InfoCard)

Biological roles:

skeletal isoform: skeletal muscle contraction: calcium binding to the low-affinity sites in the N-terminal domain of troponin C triggers this process by releasing inhibition by troponin I on formation of the actomyosin complex
biochemical evidence in Oryctolagus cuniculus: Removal of troponin C results in muscle fibers that are relaxed at all concentrations of calcium. Supplying exogenous troponin C restores calcium-dependent cotnraction. (InfoCard)

Disease states:

not yet available in the data library

Target molecules:

skeletal isoform: troponin I
structural evidence for interaction in Oryctolagus cuniculus: Troponin C is bound to a fragment of troponin I in a crystal structure (InfoCard)
effect of interaction in Oryctolagus cuniculus: Binding of calcium-loaded troponin C to troponin I relieves the inhibition of the actomyosin ATPase by troponin I (InfoCard)

Structural Information:

Calcium-coordination:
skeletal isoform, Gallus gallus:	EF1 ; X = D30 OD2; Y = D32 OD1; Z = H₂O; -X = H₂O; -Y = D36 O; -Z1 = E41 OE1; -Z2 = E41 OE2 EF2 ; X = D66 OD2; Y = D68 OD2; Z = S70 OG; -X = H₂O; -Y = T72 O; -Z1 = E77 OE1; -Z2 = E77 OE2 (InfoCard)
skeletal isoform, Gallus gallus:	EF1 ; X = D30 OD2; Y = D32 OD1; Z = H₂O; -X = H₂O; -Y = D36 O; -Z1 = E41 OE1; -Z2 = E41 OE2 EF2 ; X = D66 OD2; Y = D68 OD2; Z = S70 OG; -X = H₂O; -Y = T72 O; -Z1 = E77 OE1; -Z2 = E77 OE2 EF3 ; X = D106 OD2; Y = N108 OD1; Z = D110 OD2; -X = H₂O; -Y = F112 O; -Z1 = E117 OE1; -Z2 = E117 OE2 EF4 ; X = D142 OD2; Y = N144 OD1; Z = D146 OD2; -X = H₂O; -Y = R148 O; -Z1 = E153 OE1; -Z2 = E153 OE2 (InfoCard)

Nature of the conformational changes:
Conformational change between apo and four calcium ions bound states of skeletal isoform:	The conformational change is essentially the same as seen in calmodulin, and consists of 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)

Secondary structure: (as reported in the PDB file and its accompanying reference)
skeletal isoform, Gallus gallus, two calcium ions bound state:	Helices: pre-EF-hand 1: helix 1: 10 - 13, N-terminal domain: helix 2: 16 - 29, helix 3: 39 - 48, helix 4: 55 - 65, helix 5: 75 - 83 (pdb code 1AVS: InfoCard)
skeletal isoform, Gallus gallus, two calcium ions bound state:	Helices: pre-EF-hand 1: helix 1: 3 - 12, N-terminal domain: helix 2: 16 - 27, helix 3: 42 - 48, helix 4: 55 - 65, helix 5: 75 - 85, C-terminal domain: helix 6: 95 - 105, helix 7: 115 - 124, helix 8: 131 - 141, helix 9: 151 - 159 Beta strands: N-terminal domain: strand 1: 35 - 39, strand 2: 71 - 75, C-terminal domain: strand 3: 113, strand 4: 149 (pdb code 1TOP: InfoCard)

Additional structural information:
View a table of interhelical angles from various structures View a table of interhelical contacts from various structures View a table of hydrogen bonds observed in various structures

Available structures: (follow the links from the PDB code to the retrieve the PDB files)
Apo Structures:	1SPY: cardiac isoform, Homo sapiens, N-terminal domain, pH 6.7 NMR solution structure, 40 models, 14.55 restraints per residue (InfoCard) 1TNP: skeletal isoform, Gallus gallus, N-terminal domain, pH 6.7 NMR solution structure, 40 models, 10.07 restraints per residue (InfoCard) 1TRF: skeletal isoform, Meleagris gallopavo, N-terminal domain, NMR solution structure, 1 models (InfoCard)
Calcium Loaded Structures:	1AP4: cardiac isoform, Homo sapiens, N-terminal domain, pH 6.7 NMR solution structure, 40 models, 16.19 restraints per residue 1 Ca ion bound (InfoCard) 3CTN: cardiac isoform, Gallus gallus, C-terminal domain, pH 6.7 NMR solution structure, 30 models, 15.35 restraints per residue 2 Ca ions bound (InfoCard) 1PON: skeletal isoform, Gallus gallus, heterodimer, pH 7.19 NMR solution structure, 42 models, 11.76 restraints per residue 2 Ca ions bound (InfoCard) 1CTA: skeletal isoform, Gallus gallus, homodimer, pH 7.35 NMR solution structure, 1 models, 13.02 restraints per residue 1 Ca ion bound (InfoCard) 1AVS: skeletal isoform, Gallus gallus, N-terminal domain, pH 7.5 Crystal structure, 1.75 angstrom resolution, R-value = 21.4 2 Ca ions bound (InfoCard) 1TNW: skeletal isoform, Gallus gallus, full-length, pH 7 NMR solution structure, 23 models 4 Ca ions bound (InfoCard) 2TN4: skeletal isoform, Oryctolagus cuniculus, full length protein, pH 7.2 Crystal structure, 2 angstrom resolution, R-value = 21.2, R-free = 26.5 4 Ca ions bound (InfoCard) 1TN4: skeletal isoform, Oryctolagus cuniculus, full length protein, pH 7.2 Crystal structure, 1.9 angstrom resolution, R-value = 18.9, R-free = 26.5 4 Ca ions bound (InfoCard)
Partially Saturated Structures:	1TOP: skeletal isoform, Gallus gallus, full length protein, pH 5.1 Crystal structure, 2 angstrom resolution, R-value = 17.2 2 Ca ions bound (InfoCard)
Other Metal Bound Structures:	1NCX: skeletal isoform, Gallus gallus, full length protein, Crystal structure, 1.8 angstrom resolution, R-value = 16 2 Cd ions bound (InfoCard) 1NCY: skeletal isoform, Gallus gallus, full length protein, Crystal structure, 2.1 angstrom resolution, R-value = 13 2 Mn ions bound (InfoCard) 1NCZ: skeletal isoform, Gallus gallus, full length protein, Crystal structure, 1.8 angstrom resolution, R-value = 19 2 Tb ions bound (InfoCard)
Mutant Structures:	1SMG: skeletal isoform, Gallus gallus, N-terminal domain, pH 6.7 NMR solution structure, 40 models, 16.38 restraints per residue 2 Ca ions bound Mutations: E41A (InfoCard)

Information about mutants:

E41A (skeletal isoform, Gallus gallus)