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NetGlycate - 1.0

Glycation of ε amino groups of lysines in mammalian proteins

The NetGlycate 1.0 server predicts glycation of ε amino groups of lysines in mammalian proteins.

For a description of the data set used to develop the NetGlycate method see here.

Note: This service has a high failure rate, due to a dependency on an old program. If your run fails, submit your sequences again. This does not affect the results.

Submission

Restrictions:
At most 2,000 sequences and 200,000 amino acids per submission; each sequence not more than 4,000 and no less than 34 amino acids.

Confidentiality:
The sequences are kept confidential and will be deleted after processing.

CITATIONS:

For publication of results, please cite:

Analysis and prediction of mammalian protein glycation.
Morten Bo Johansen, Lars Kiemer and Søren Brunak
Glycobiology, 16:844-853, 2006.

PMID: 16762979 doi: 10.1093/glycob/cwl009

Instructions

1. Specify the input sequences

All the input sequences must be in one-letter amino acid code. The allowed alphabet (not case sensitive) is as follows:

A C D E F G H I K L M N P Q R S T V W Y and X (unknown)

All the other symbols will be converted to X before processing. The sequences can be input in the following two ways:

Paste a single sequence (just the amino acids) or a number of sequences in FASTA format into the upper window of the main server page.
Select a FASTA file on your local disk, either by typing the file name into the lower window or by browsing the disk.

Both ways can be employed at the same time: all the specified sequences will be processed. However, there may be not more than 2,000 sequences and 200,000 amino acids in total in one submission. The sequences longer than 4,000 amino acids will be ignored.

2. Customize your run

By default the server produces graphical output illustrating the predictions (in GIF). The graphs can be very valuable for locating the "hot" spots in your protein. The generation of graphics can be disabled by un-checking the button labelled 'Generate graphics'.

3. Submit the job

Click on the "Submit" button. The status of your job (either 'queued' or 'running') will be displayed and constantly updated until it terminates and the server output appears in the browser window.

At any time during the wait you may enter your e-mail address and simply leave the window. Your job will continue; you will be notified by e-mail when it has terminated. The e-mail message will contain the URL under which the results are stored; they will remain on the server for 24 hours for you to collect them.

Format of NetGlycate-1.0 output

DESCRIPTION

For each input sequence the length and the name of the sequence are stated followed by a table with the prediction results. There is a table row for each lysine residue in the sequence; the columns are:

sequence name, truncated to 20 characters;
residue position in the sequence;
score, a number between -1 and 1; when the score is above 0 the residue is a predicted glycation site;
the word "glycate";
answer: either the word "YES" or a dot ("."), reflecting the score.

After the table, the whole sequence is printed alongside a summary of the predicted glycation sites and their positions.

Finally, if the 'Generate graphics' button has been checked, the server displays a figure in GIF showhing a plot of the score for each lysine residue against the sequence position of that residue.

EXAMPLE OUTPUT

The example below shows the output for the UniProt entry P19111 (PPBI_BOVIN), an intestinal alkaline phosphatase precursor whose activity is known to be inhibited by glycation ( McCarthy et al. 1998). At this point (Feb 2006) the glycation sites have not been determined experimentally and published.

>PPBI_BOVIN 533 amino acids # # netglycate-1.0 prediction results # # Sequence # Score Answer # ----------------------------------------------------------- # PPBI_BOVIN 43 -0.917 glycate . # PPBI_BOVIN 44 -0.883 glycate . # PPBI_BOVIN 53 -0.653 glycate . # PPBI_BOVIN 75 0.567 glycate YES # PPBI_BOVIN 81 -0.808 glycate . # PPBI_BOVIN 100 0.817 glycate YES # PPBI_BOVIN 123 -0.587 glycate . # PPBI_BOVIN 141 0.803 glycate YES # PPBI_BOVIN 156 -0.711 glycate . # PPBI_BOVIN 157 -0.864 glycate . # PPBI_BOVIN 160 -0.885 glycate . # PPBI_BOVIN 224 -0.837 glycate . # PPBI_BOVIN 247 0.491 glycate YES # PPBI_BOVIN 249 -0.704 glycate . # PPBI_BOVIN 259 -0.879 glycate . # PPBI_BOVIN 294 -0.825 glycate . # PPBI_BOVIN 303 0.972 glycate YES # PPBI_BOVIN 342 -0.845 glycate . # PPBI_BOVIN 359 -0.950 glycate . # PPBI_BOVIN 400 0.721 glycate YES # PPBI_BOVIN 405 -0.521 glycate . # MQGACVLLLLGLHLQLSLGLVPVEEEDPAFWNRQAAQALDVAKKLQPIQT # 50 AAKNVILFLGDGMGVPTVTATRILKGQMNGKLGPETPLAMDQFPYVALSK # 100 TYNVDRQVPDSAGTATAYLCGVKGNYRTIGVSAAARYNQCKTTRGNEVTS # 150 VMNRAKKAGKSVGVVTTTRVQHASPAGAYAHTVNRNWYSDADLPADAQMN # 200 GCQDIAAQLVNNMDIDVILGGGRKYMFPVGTPDPEYPDDASVNGVRKRKQ # 250 NLVQAWQAKHQGAQYVWNRTALLQAADDSSVTHLMGLFEPADMKYNVQQD # 300 HTKDPTLQEMTEVALRVVSRNPRGFYLFVEGGRIDHGHHDDKAYMALTEA # 350 GMFDNAIAKANELTSELDTLILVTADHSHVFSFGGYTLRGTSIFGLAPSK # 400 ALDSKSYTSILYGNGPGYALGGGSRPDVNDSTSEDPSYQQQAAVPQASET # 450 HGGEDVAVFARGPQAHLVHGVEEETFVAHIMAFAGCVEPYTDCNLPAPTT # 500 ATSIPDAAHLAASPPPLALLAGAMLLLLAPTLY # 550 %1 .................................................. # 50 %1 ........................G........................G # 100 %1 ........................................G......... # 150 %1 .................................................. # 200 %1 ..............................................G... # 250 %1 .................................................. # 300 %1 ..G............................................... # 350 %1 .................................................G # 400 %1 .................................................. # 450 %1 .................................................. # 500 %1 .................................

References

Analysis and prediction of mammalian protein glycation.
Morten Bo Johansen, Lars Kiemer and Søren Brunak
Glycobiology, 16:844-853, 2006

PMID: 16762979 doi: 10.1093/glycob/cwl009

Center for Biological Sequence Analysis, BioCentrum-DTU, The Technical University of Denmark, DK-2800 Lyngby, Denmark

Abstract

Glycation is a nonenzymatic process in which proteins react with reducing sugar molecules and thereby impair the function and change the characteristics of the proteins. Glycation is involved in diabetes and aging where accumulation of glycation products causes side effects. In this study, we statistically investigate glycation of ε amino groups of lysines and also train a sequence-based predictor. The statistical analysis suggests that acidic amino acids, mainly glutamate, and lysine residues catalyze the glycation of nearby lysines. The catalytic acidic amino acids are found mainly C-terminally from the glycation site, whereas the basic lysine residues are found mainly N-terminally. The predictor was made by combining 60 artificial neural networks in a balloting procedure. The cross-validated Matthews correlation coefficient for the predictor is 0.58 which is quite impressive given the relatively small amount of experimental data available.

GETTING HELP

If you need help regarding technical issues (e.g. errors or missing results) contact Technical Support. Please include the name of the service and version (e.g. NetPhos-4.0). If the error occurs after the job has started running, please include the JOB ID (the long code that you see while the job is running).

If you have scientific questions (e.g. how the method works or how to interpret results), contact Correspondence.

Correspondence: Technical Support: