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Ortholog conservation Domain conservation Secondary structure 3D structure More Home

Analysis of p.(Tyr95Cys) 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 Y95	Conservation - gap
  24	76.99%	89.49%	0 details	0 details	0 details	24 / 24 (100.00%)	24 / 24 (100.00%)

  
  
  

  The alignment does not show any divergent sequences.

  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 95). 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.

  Informativity of this alignment: P₀ = 0.0150, with an average substitution per position of 4.20.
  This means that you have a probability of 0.9850 (98.50%) that position 95 is invariant because it is functionally constrained.
  More information here.

  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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  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 residue belongs to the domain Motor domain.

  1

  729

  	A >700 residues domain in myosin VIIa, which is able to bind ATP and generates movements along actin filaments.

  
  
  
  
  

  Motor domain of myosin VIIa domain alignment including p.Y95 residue.

  
  
  

  Number of sequences	AAPID*** (from aa 1 to aa 729)	AAPIR!	Number of divergencies	Number of mutant	Number of gaps	Conservation of Y95	Conservation - gap
  1623	39.88%	78.91%	118 details	0	690	815 / 1623 (50.22%)	815 / 933 (87.35%)

  
  
  

  Divergencies

  Residues present in more than 10% of the sequences are highlighted in blue.

  A - 0.99%

  F - 3.39%

  H - 1.48%

  K - 0.06%

  Q - 1.17%

  R - 0.06%

  S - 0.06%

  V - 0.06%

  ***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
  ^!AAPIR is here compared with AAPID.

  Show Venn diagram of alignment

  Display WebLogo for the region

  Click on the top-left corner to enlarge.

  

  Display complete alignment (Clustal format)

  Display region alignment (21 residues, Fasta format)

  Display methods

  Alignments have all been extracted from Prosite⁽⁴⁾, except alignment of vlgr1 calx-beta domains which comes from Pfam⁽⁵⁾. Pictures of proteins have been performed using MyDomains - Image Creator. WebLogos are drawn with WebLogo 3⁽¹⁴⁾

• Secondary structure analysis:

  Residu Y95 is predicted to belong to a β strand. Probability is 0.687.

  Direct environment is as follow:

  D	H	L	I	Y95	T	Y	T	G

  
  
  

  Observed frequencies in β strands:
  Y: 1.37
  C: 1.41

  The two residues are found equivalent 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 Y95 to be located in a β strand (which confirms PsiPred prediction) and C95 in a β strand.
    Moreover, the residue is located at the beginning of this β strand (which contains 4 residues).
    
    
  • The wild type residue is predicted to be buried and the mutant residue to be buried.
    
    
  • Hydrogen bond network:
    
    

    Y95	C95
    distance: 3.22 Å / angle: 2.91 rad between O and ARG 88 NH2	distance: 3.27 Å / angle: 2.86 rad between O and ARG 88 NH2

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

    Y95	C95
    none	4.89 Å between CB and ILE 94 CB 4.33 Å between CB and LEU 102 CG

    
    
    

  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.
    
    

    Y95	C95
    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.
    
    
    
    
    

    Y95 (wild-type)	C95 (mutant)

    
                  Spin on/off       Sharper/Faster              Change background             

    
    JSmol Legends:
    The residue at the position 95 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 95 are labelled in blue.
    Amino acids involved in steric clashes with the residue 95 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 95    
    
    
    
    
  • Graphical display of the region at NCBI (including SNPs)

See accession numbers of sequences used or references.

Execution time: 11 wallclock secs ( 7.38 usr 0.04 sys + 2.45 cusr 1.33 csys = 11.20 CPU)