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Ortholog conservation Domain conservation Secondary structure 3D structure More Home

Analysis of p.(Glu1327Lys) 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 E1327	Conservation - gap
  24	76.99%	97.39%	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 1327). 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 1327 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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  Anolis carolinensis

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  Taeniopygia guttata

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  Danio rerio

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  Drosophila melanogaster

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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 FERM 1 of myosin VIIa is very likely to interact with:

  • sans - central

  The residue belongs to the domain FERM 1.

  1258

  1602

  	FERM domains (~ 300 residues) have various roles, and the partner(s) of myosin VIIa remain(s) to identify.

  
  
  
  
  

  FERM 1 of myosin VIIa domain alignment including p.E1327 residue.

  
  
  

  Number of sequences	AAPID*** (from aa 1258 to aa 1602)	AAPIR!	Number of divergencies	Number of mutant	Number of gaps	Conservation of E1327	Conservation - gap
  162	20.81%	18.50%	143 details	74	1	18 / 162 (11.11%)	18 / 161 (11.18%)

  
  
  

  Divergencies

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

  A - 3.70%	D - 0.62%	F - 0.62%	H - 10.49%	I - 0.62%	K - 45.68%	L - 3.09%	M - 4.32%	N - 2.47%	Q - 1.85%
  R - 9.88%	S - 3.70%	T - 1.23%

  If we just consider FERM domain of myosin VIIa, we can add that:
  
  on 2 sequences, conservation is 1/2 (50.00%),
  or 1/2 (50.00%) if you do not take the gaps into account.

  ***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 E1327 is predicted to belong to an α helice. Probability is 0.787.

  Direct environment is as follow:

  I	S	Q	C	E1327	Q	Y	A	K

  
  
  

  Observed frequencies in α helices:
  E: 1.2
  K: 1.08

  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
    3PVL	97.9 %	2/334 - 0.6 %	5/398 - 1.3 %	387/398 - 97.2 %

    * 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 13 α helices and of 10 β strands (and is mainly composed of helices (183 residues in helices against 58 in strands, for a total of 402 amino acids)).
    
    
  • 3D model predicts E1327 to be located in an α helice (which confirms PsiPred prediction) and K1327 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 1.12 and 1.11.
    A potential Side chain interaction of the type i,i+4 has been detected between wild-type residue and LYS1331.
    This interaction presents an attracting energy of -0.44 kcal/mol.
    A potential Side chain interaction of the type i,i+4 has been detected between mutant residue and LYS1331.
    This interaction presents an attracting energy of 0.17 kcal/mol.
    The change increases the interaction.
    A potential Side chain interaction of the type i,i-4 has been detected between mutant residue and ILE1323.
    This interaction presents an attracting energy of -0.22 kcal/mol.
    
    
  • The wild type residue is predicted to be buried and the mutant residue to be buried.
    
    
  • The mutant residue is predicted to alter the hydrogen bond network.
    
    

    E1327

    K1327

    distance: 3.01 Å / angle: 2.55 rad between O and LYS 1331 N distance: 3.04 Å / angle: 2.75 rad between N and ILE 1323 O distance: 3.46 Å / angle: 1.71 rad between O and ALA 1330 N distance: 2.94 Å / angle: 1.73 rad between OE1 and TRP 1246 N distance: 3.09 Å / angle: 1.61 rad between OE2 and TRP 1246 N distance: 3.42 Å / angle: 2.14 rad between OE2 and SER 1245 OG distance: 3.30 Å / angle: 1.81 rad between N and SER 1324 O

    distance: 3.06 Å / angle: 2.50 rad between O and LYS 1331 N distance: 3.03 Å / angle: 2.74 rad between N and ILE 1323 O distance: 3.28 Å / angle: 1.81 rad between N and SER 1324 O distance: 3.16 Å / angle: 2.53 rad between NZ and GLU 1337 O

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

    E1327	K1327
    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.
    
    
    
    
    

    E1327 (wild-type)	K1327 (mutant)

    
                  Spin on/off       Sharper/Faster              Change background             

    
    JSmol Legends:
    The residue at the position 1327 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 1327 are labelled in blue.
    Amino acids involved in steric clashes with the residue 1327 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 1327    
    
    
    
    
  • Graphical display of the region at NCBI (including SNPs)

See accession numbers of sequences used or references.

Execution time: 3 wallclock secs ( 1.25 usr 0.01 sys + 1.80 cusr 0.62 csys = 3.68 CPU)