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Ortholog conservation Domain conservation Secondary structure 3D structure More Home

Analysis of p.(Arg873Trp) variant, MYO7A gene, myosin VIIa protein (2215 residues)

• Ortholog conservation:

  
  
  

  Number of sequences	AAPI*	AAPIR**	Number of divergencies	Number of mutant	Number of gaps	Conservation of R873	Conservation - gap
  24	76.99%	62.02%	3 details	0 details	0 details	21 / 24 (87.50%)	21 / 24 (87.50%)

  
  
  

  Divergencies:

  Caenorhabditis elegans - P

  Ciona savignyi - K

  Ciona intestinalis - K

  The mutant residue cannot be found in the alignment.

  There is no gap in the alignment.

  *AAPI: Alignment Average Percentage Identity
  **AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 873). AAPIR appears in green if it is more than 10% compared to AAPI, in red if less than 10%.

  You can check the AAPIRs compared with AAPI of the whole alignment by clicking here. The help page will tell you more.

  Display alignment

  Click on the alignment to zoom in and out.

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  Homo sapiens

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  Pan troglodytes

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  Macaca mulatta

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  Felis catus

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  Cavia porcellus

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  Mus musculus

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  Rattus norvegicus

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  Canis familiaris

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  Bos taurus

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  Equus caballus

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  Monodelphis domestica

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  Anolis carolinensis

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  Gallus gallus

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  Taeniopygia guttata

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  Tetraodon nigroviridis

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  Danio rerio

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  Oryzias latipes

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  Takifugu rubripes

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  Gasterosteus aculeatus

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  Aedes aegypti

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  -

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  Drosophila melanogaster

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  Caenorhabditis elegans

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  Ciona savignyi

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  Ciona intestinalis

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  Species color legend (basic classification):

  Great apes | Other monkeys | Prosimians | Other mammals | Lizards | Birds | Amphibians | Fishes | Insects | Nematods | Tunicates | Echinoderms

  Show Venn diagram of alignment

  Display WebLogo for the region

  Click on the top-left corner to enlarge.

  

  Display alignment phylogenetic tree

  Click on the top-left corner to enlarge.

  
  

  Download tree in Newick format (right-click on the link, and choose 'Save target as').

  Display region alignment (21 residues, Fasta format)

  Display methods

  Ortholog sequences have been selected from the Ensembl⁽¹⁾ and NCBI websites. Alignment has been performed with ClustalW⁽²⁾, version 1.83 or 2.0.7. Trees have been built using Phylogeny.fr ⁽³⁾, based on the alignments. Software used is PhyML 3.0 aLRT with default parameters. Pictures of trees have been made using Phylip at Mobyle. AAPI and AAPIR have been calculated thanks to Bioperl. WebLogos are drawn with WebLogo 3⁽¹⁴⁾

  Accession numbers

• Domain conservation:

  The domain Coiled coil of myosin VIIa is very likely to interact with:

  • myosin VIIa - Coiled coil

  The residue belongs to the domain Coiled coil.

  858

  935

  	Coiled coils domain are composed of heptad repeats hpphppp (h hydrophobic, p polar). They adopt an alpha helice conformation and can be used for dimerization.

  
  
  
  
  

  There are no alignments available concerning the domain Coiled coil of the protein myosin VIIa or the residue is not present in the alignment.

• Secondary structure analysis:

  Residu R873 is predicted to belong to an α helice. Probability is 0.984.

  Direct environment is as follow:

  A	E	K	M	R873	L	A	E	E

  
  
  

  Observed frequencies in α helices:
  R: 1.11
  W: 0.98

  Mutant residu is less observed in this type of structure.

  Display methods

  Predictions of secondary structures have been made with PsiPred⁽⁹⁾ , version 2.5, using Protein Multiple Sequences Alignments as input, in order to increase the accuracy of the prediction. Amino acid frequencies have been calculated from a non redondant set defined by the RCSB. Details are provided here.

• 3D analysis:

  Models provided and analysed by USMA must be considered as predictions, therefore be careful when interpreting the results. All efforts have been made to build structures of quality, however, they are provided with NO WARRANTY as to their accuracy with the real biological molecules studied.

  Predicted wild type and mutant structures have been compared. You will find the results below. Please note that USMA's "3D engine" is unable to analyse interactions with non amino-acids molecules (e.g. ATP or Ca²⁺).

  • Quick assessment of the overall quality of the structure:
    
    

    PDB template	Sequence identity*	Molprobity bad rotamers	Molprobity Ramachandran outliers	Molprobity Ramachandran favored
    2DFS	37 %	21/836 - 2.5 %	8/955 - 0.8 %	924/955 - 96.8 %

    * between target and template

    Otherwise, see detailed Molprobity output

    
    
  • Download wild-type model (PDB format) or mutant prediction.
    
    
  • Check 3D coverage of myosin VIIa.
    
    
  • This model is made of 38 α helices and of 9 β strands (and is mainly composed of helices (455 residues in helices against 61 in strands, for a total of 957 amino acids)).
    
    
  • 3D model predicts R873 to be located in an α helice (which confirms PsiPred prediction) and W873 in an α helice.
    Moreover, the residue is located in the core of this α helice (which contains 15 residues).
    Helix interior propensities of wild-type and mutant residues are 1.28 and 1.03.
    
    
  • The wild type residue is predicted to be exposed and the mutant residue to be exposed.
    
    
  • The 2 residues have a different polarity.
    
    
  • The two residues have different charges, which can interfere with ionic bonds or potential inter- or intra-molecular interactions.
    
    
  • The mutant residue is predicted to alter the hydrogen bond network.
    
    

    R873	W873
    distance: 3.09 Å / angle: 2.72 rad between N and ALA 869 O distance: 3.16 Å / angle: 1.92 rad between N and GLU 870 O distance: 3.24 Å / angle: 1.82 rad between O and GLU 876 N	distance: 3.11 Å / angle: 2.73 rad between N and ALA 869 O distance: 3.18 Å / angle: 1.93 rad between N and GLU 870 O

    
    
    
  • The mutant residue is predicted to modify the hydrophobic interaction network.
    
    

    R873	W873
    none	4.65 Å between CG and LEU 874 CD2 4.87 Å between CD2 and LEU 874 CG 4.83 Å between CD1 and LEU 874 CD2 4.90 Å between CE2 and LEU 874 CG 4.29 Å between CE3 and LEU 874 CD2 4.05 Å between CZ2 and LEU 874 CD2 4.33 Å between CZ3 and LEU 874 CD2 4.21 Å between CH2 and LEU 874 CD2

    
    
    

  For hydrophobic effect, only one potential "interaction" per atom of the residue of interest with another residue is shown. The important point is more to check if residue X and Y (and Z...) are likely to form an hydrophobic pocket than the exact number of "interactions".

  • The mutant residue is not predicted to introduce steric clashes.
    
    

    R873	W873
    none	none

    
    
    
  • Pictures:
    Click on the top-left corner to enlarge.
    Legend: non-covalent bonds/steric clashes: - - - - colors: - - - -: h-bonds, - - - -: ionic bonds, - - - -: hydrophobic interactions; - - - -:clashes.
    
    
    
    
  • If you are not satisfied with the pictures above, or just want to investigate further the structures, you can display the JSmol applet of the wild-type (left) and mutant (right) structures.
    
    Click on the JSmol applet's link to hide it.
    You have a full access to Jmol commands with a simple right click on one applet.
    
    
    
    
    

    R873 (wild-type)	W873 (mutant)

    
                  Spin on/off       Sharper/Faster              Change background             

    
    JSmol Legends:
    The residue at the position 873 is located in the center, labelled in yellow and surrounded by its neighboring residues (distance < 5 Å).
    Amino acids involved in H-bonds with the residue 873 are labelled in blue.
    Amino acids involved in steric clashes with the residue 873 are labelled in red.

    Display methods

    All 3D structures except two for harmonin and sans, and myosin VIIa and sans used in USMA are predictions. They are build by homology, (more), using Domain Fishing⁽¹⁵⁾ or Atome 2⁽²⁵⁾ for template recognition, modeller⁽¹⁶⁾ for model building and mutation, and PyMOL⁽¹⁷⁾ and Jmol⁽¹⁸⁾ for visualisation. Each structure has been assessed with MolProbity⁽¹⁹⁾. Msms⁽²⁰⁾ is used to calculate solvent accessibility, and STRIDE⁽²¹⁾ (plus stride2pdb) for secondary structure assignment. When necessary, SCWRL4⁽²²⁾ was used to refine side chains conformations.
    Secondary structure analyses in 3D models uses side chain interaction energies reviewed in ⁽²³⁾, as well as amino-acids propensities for N-caps, N1-N3, helix middle, C3-C1 and C-caps extracted from ⁽²⁴⁾(PDB values).

• Additional ressources:

  
  
  
  • UNIPROT annotations
    

    The variation is not reported in Uniprot.

  • Click on the LOVD picture to check if a variant is described at position 873    
    
    
    
    
  • Graphical display of the region at NCBI (including SNPs)

See accession numbers of sequences used or references.

Execution time: 9 wallclock secs ( 6.90 usr 0.01 sys + 1.57 cusr 0.33 csys = 8.81 CPU)