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Revision as of 11:29, 26 June 2011 by Uskat (talk | contribs) (Conservation Analysis with Multiple Alignments)

General Information

SNP-id rs121907974
Codon 211
Mutation Codon Phe -> Ser
Mutation Triplet TTC -> TCC

Pysicochemical Properities

First of all, we explored the amino acid properties and compared them for the original and the mutated amino acid. Therefore we created the possible effect that the mutation could have on the protein.

Phe Ser consequences
polar, tiny, hydrophilic, neutral aliphatic, hydrophobic, neutral Ile is much bigger than Ser and also is branched, because it is an aliphatic amino acid. Therefore the structure of both amino acids is really different and Ile is to big for the position where Ser was. Therefore, there has to be a big change in the 3D structure of the protein and the protein probably will loose its function.

Visualisation of the Mutation

In the next step, we created the visualization of the muation with PyMol. Therefore we created a picture for the original amino acid, for the new mutated amino acid and finally for both together in one picture whereas the mutation is white colored. The following pictures display that the mutated amino acid Serine looks very different to Phenylalanine. Phenylalanine has a huge aromatical ring. Contrary, Serine is very smaller and differs a little bit in the orientation. This shows that the amino acids have huge structural differences which will probably cause drastical effects on protein structure and function.

picture original aa picture mutated aa combined picture
Amino acid Phenylalanine
Amino acid Serine
Picture which visualize the mutation

Subsitution Matrices values

PAM 1 Pam 250 BLOSOUM 62
value aa most frequent substitution rarest substitution value aa most frequent substitution rarest substitution value aa most frequent substitution rarest substitution
2 28 (Tyr) 0 (Asp, Cys, Glu, Lys, Pro, Val) 2 20 (Tyr) 1 (Arg, Asp, Cys, Gln, Glu, Gly, Lys, Pro) -2 3 (Tyr) -4 (Pro)

PSSM analysis

self-information expected self-information
Phe 6 38
Ser -5 0

Conservation Analysis with Multiple Alignments

As a next step we created a multiple alignment which contains the HEXA sequence and 9 other mammalian homologous sequences from uniprot. Afterwards we looked at the position of the different mutations and looked at the conservation level on this position. The regarded mutation is presented by the first colored column. Here we can see, that the all other mammalians have on this position the amino acid Phenylalanine. Therefore, the mutation on this position is highly conserved and a mutation there will cause probably huge structural and functional changes for the protein.

Mutation in the multiple alignment

Secondary Structure Mutation Analysis


Comparison with the real structure:

Mutation at position 211
Mutation at position 211 - detailed view

SNAP Prediction

Substitution Prediction Reliability Index Expected Accuracy
S Non-neutral 5 87%

A detailed list of all possible substitutions can be found [here]

SIFT Prediction

SIFT Matrix:
Each entry contains the score at a particular position (row) for an amino acid substitution (column). Substitutions predicted to be intolerant are highlighted in red.

Sift legend.png
211 sift.png.png

SIFT Table
Threshold for intolerance is 0.05.
Amino acid color code: nonpolar, uncharged polar, basic, acidic.
Capital letters indicate amino acids appearing in the alignment, lower case letters result from prediction.

Predict Not ToleratedPositionSeq RepPredict Tolerated

PolyPhen2 Prediction

HumDiv prediction
HumVar prediction