Fabry:Sequence-based analyses

Fabry Disease » Sequence-based analyses

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The following analyses were performed on the basis of the α-Galactosidase A sequence. Please consult the journal for the commands used to generate the results.

Signal peptides

predicts the presence and location of signal peptide cleavage sites in amino acid sequences

α-Galactosidase A (P06280)

<figure id="fig:1r46_SP">

Human α-Galactosidase A, plot of scores for signal peptide cleavage site (source)

</figure>

organism: Homo sapiens (Human)
pdb-id: 1r46
Signal-peptide: 1-31
Signal-peptide sequence: MQLRNPELHLGCALALRFLALVSWDIPGARAL
As already described in section Transmembrane helices the human α-Galactosidase A does not have transmembrane helical structures and from our background knowledge we know that the protein has a 31 residues long signal peptide at the N-terminus. The protein's pdb structure is available only without signal peptide, since those residues are cleaved off. Therefore no picture is provided here.
In <xr id="fig:1r46_SP"/> the signal peptide prediction of SignalP 4.0 is shown. The cleaved site is clearly indicated after residue 31, since the S-score (green) drops and the C- (red) and Y-score (blue) not only have a peak at this position, but attain their maximum at this point (see SignalP output file )

Serum Albumin (P02768)

organism: Homo sapiens (Human)
pdb-id: 1ao6
Signal-peptide: 1-18
Signal-peptide sequence: MKWVTFISLLFLFSSAYS

Lysosome-associated membrane glycoprotein 1 (P11279)

organism: Homo sapiens (Human)
pdb-id: na
Signal-peptide: 1-28
Signal-peptide sequence: MAAPGSARRPLLLLLLLLLLGLMHCASA

Aquaporin-4 (P47863)

organism: Rattus norvegicus (Rat)
pdb-id: 2d57
Signal-peptide: none
Signal-peptide sequence: ---

GO terms

GOPET

Searching the GOPET annotation tool with the AGAL_HUMAN sequence revealed 5 GOIds, which are displayed in <xr id="tab:GOPET"/>. On a first glance, since we already know the name and function of the protein, it is a bit surprising, that alpha-galactosidase activity is only the third entry with 96% confidence. In our already carried out information gathering we learned that α-galactosidase A is a hydrolase thus the first three entries were not surprising. Considering that our enzyme mainly is a glycosidase, the both entries on top of the list make perfekt sense.
Again a bit surprising was the last entry. α-N-Acetylgalactosaminidase is actually used for enzyme replacement therapy, which we mention on our main page. The structure of both enzymes is similar to each other, but this still does not explain the association of this GO term to the AGAL protein.

<figtable id="tab:GOPET"> The results of the GOPET search

Result for GOPET search
GOid	Aspect	Confidence	GO term
GO:0016798	Molecular Function Ontology (F)	98%	hydrolase activity acting on glycosyl bonds
GO:0004553	Molecular Function Ontology (F)	98%	hydrolase activity hydrolyzing O-glycosyl compounds
GO:0016787	Molecular Function Ontology (F)	97%	hydrolase activity
GO:0004557	Molecular Function Ontology (F)	96%	alpha-galactosidase activity
GO:0008456	Molecular Function Ontology (F)	89%	alpha-N-acetylgalactosaminidase activity

</figtable>

ProtFun2.0

EC=3.2.1.22(EC 3.-.-.- Hydrolase)
Predicted: EC 6.-.-.-(Ligase)

############## ProtFun 2.2 predictions ##############

>gi_4504009_

# Functional category                  Prob     Odds
  Amino_acid_biosynthesis              0.283   12.847
  Biosynthesis_of_cofactors            0.339    4.708
  Cell_envelope                     => 0.652   10.690
  Cellular_processes                   0.057    0.783
  Central_intermediary_metabolism      0.400    6.343
  Energy_metabolism                    0.151    1.678
  Fatty_acid_metabolism                0.032    2.448
  Purines_and_pyrimidines              0.506    2.082
  Regulatory_functions                 0.013    0.083
  Replication_and_transcription        0.047    0.175
  Translation                          0.211    4.807
  Transport_and_binding                0.549    1.339

# Enzyme/nonenzyme                     Prob     Odds
  Enzyme                            => 0.805    2.811
  Nonenzyme                            0.195    0.273

# Enzyme class                         Prob     Odds
  Oxidoreductase (EC 1.-.-.-)          0.176    0.845
  Transferase    (EC 2.-.-.-)          0.195    0.564
  Hydrolase      (EC 3.-.-.-)          0.244    0.769
  Lyase          (EC 4.-.-.-)          0.029    0.608
  Isomerase      (EC 5.-.-.-)          0.010    0.321
  Ligase         (EC 6.-.-.-)       => 0.141    2.776

# Gene Ontology category               Prob     Odds
  Signal_transducer                    0.090    0.419
  Receptor                             0.014    0.083
  Hormone                              0.002    0.318
  Structural_protein                   0.004    0.127
  Transporter                          0.024    0.222
  Ion_channel                          0.010    0.169
  Voltage-gated_ion_channel            0.003    0.127
  Cation_channel                       0.010    0.215
  Transcription                        0.047    0.367
  Transcription_regulation             0.026    0.204
  Stress_response                      0.049    0.552
  Immune_response                      0.012    0.136
  Growth_factor                        0.006    0.412
  Metal_ion_transport                  0.009    0.020

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