Canavan Task 3 - Sequence-based predictions

From Bioinformatikpedia
Revision as of 13:45, 14 May 2012 by Vorbergs (talk | contribs) (P35462)
Oh, I would sing of mackerel skies,
And why the sea is wet,
Of jelly-fish and conger-eels,
And things that I forget. 

(taken from "The Cumberbunce" by Paul West)

Protocol

Commands, Source Code and other methodocial issues are kept in the protocoll.


Secondary Structure Prediction

Information on Proteins

//TODO: pics
Identifier P10775 Q08209 Q9X0E6
Protein Ribonuclease inhibitor Serine/threonine phosphatase (alt. name:Calcineurin Divalent-cation tolerance protein
Organism Sus scrofa (pig) Homo Sapiens Thermotoga maritima
Sequence length 456 521 101
Subcellular location Cytoplasm Nucleus Cytoplasm
PDB Identifier 2BNH 1AUI 1O5J
Structure CD 3PBL.jpg CD 1ORQ.jpg CD 2D57.jpg

Prediction of disordered regions

Transmembrane Helix Prediction

Information on Proteins

Identifier P35462 Q9YDF8 P47863
Protein D(3) dopamine receptor Voltage-gated potassium channel Aquaporin-4
Organism Homo sapiens (Human) Aeropyrum pernix Rattus norvegicus (Rat)
Sequence length 400 295 323
Subcellular location Cell membrane; Multi-pass membrane protein Cell membrane; Multi-pass membrane protein Membrane; Multi-pass membrane protein
PDB Identifier 3PBL 1ORQ 2D57
Structure CD 3PBL.jpg CD 1ORQ.jpg CD 2D57.jpg

TM prediction of our Protein yielded the expected prediction of only cytoplasmic residues.


P35462

<figure id="CD_tm_3pbl">

<xr nolink id="CD_tm_3pbl"/>

</figure>

Polyphobius found 7 TMH for P35462. This is in accordance with the annotation for transmembrane regions in UniProt. There is only one structure listed for P35462: 3pbl. The annotation for TMH for this structure found in PDBTM and OPM also agrees with the Polyphobius result.

In <xr id="CD_tm_3pbl"/> the length distribution for the predicted and annotated TMH is depicted. One can see that PDBTM in general finds shorter TMH, whereas Polyphobius and OPM find longer helices.




P47863

<figure id="CD_tm_2D57">

<xr nolink id="CD_tm_2D57"/>

</figure>

Polyphobius found 6 TMH for P47863. This is in accordance with the annotation for transmembrane regions in UniProt. There are three structures listed for P47863:

  • 2D57 X-ray 3.20 A
  • 2ZZ9 X-ray 2.80 A
  • 3IYZ electron microscopy 10.00 A

Since 2ZZ9 is a mutant, we decided use 2D57 for comparison with the Phobius Output. Interestingly, OPM lists 8 TMH for P47863, whereas PDBTM agrees with the UniProt annotation and the Polyphobius output. The two additional TMH found by OPM are rather short (<10 AA) and therefore might be neglected. For the remaining TMH, all three methods find TMH of about the same length. In <xr id="CD_tm_2D57"/> the length distribution for the predicted and annotated TMH is depicted.

Q9YDF8

<figure id="CD_tm_Q9YDF8">

<xr nolink id="CD_tm_Q9YDF8"/>

</figure>

For Q9YDF8, Polyphobius did not find any homologues with the blast search. Therefore, no homolgy information could be used for the TMH prediction. In UniProt one can find the annotation for 6 TM regions and 2 intramembrane regions for this protein and lists four structures:

  • 1ORQ X-ray 3.20 A 31-253
  • 1ORS X-ray 1.90 A 33-160
  • 2A0L X-ray 3.90 A 20-259
  • 2KYH NMR - 19-160

Since in 1ORS, only residues 33-160 have been crystalized, we decided to use 1ORQ for comparison with the Polyphobius output.

Polyphobius finds 7 TMH, which correlates with the UniProt annotation:

UniProtPolyphobius
39 – 6342-60
68 – 9268-88
109 – 125108-129
129 – 145137-157
160 – 184163-184
196 – 208(intramembrane)196-213
222 – 253224-244


However, OPM and PDBTM list very diverse results. There is only a consensus on TMH 5 and 7. In <xr id="CD_tm_Q9YDF8"/> the length distribution for the TMH prediction is presented.

When comparing the annotation of OPM for the two structures 1orq and 1ors, one can find tremendous differences:

  • 1ors: C - Tilt: 19° - Segments: 1(25-46), 2(55-78), 3(86-97), 4(100-107), 5(117-148)
  • 1orq: C - Tilt: 31° - Segments: 1(153-172), 2(183-195), 3(207-225)

Yet, both annotations taken together represent the identified TMH found with Phobius (if one takes into account a shift of +12).

Signal Peptide Prediction

Information on Proteins

Identifier P02768 P11279 P47863
Protein Serum albumin Lysosome-associated membrane glycoprotein 1 Aquaporin-4
Organism Homo sapiens (Human) Homo sapiens (Human) Rattus norvegicus (Rat)
Sequence length 609 417 323
Subcellular location Secreted Lysosome membrane, Single-pass type I membrane protein Membrane; Multi-pass membrane protein
PDB Identifier 1E7I - 2D57
Structure CD 1E7I.jpg CD 2D57.jpg


GO terms and Pfam

Pfam

AstE_AspA family: Succinylglutamate desuccinylase / Aspartoacylase family