MnM - Minimotif Miner

Sample Analysis of Prion Protein (NP_000302)

Prion Protein

We have analyzed Prion protein (NP_000302). Prion is an interesting example because a D178N mutation causes disease {}. Allelic variation of the 128 position determines whether individuals get Creutzfeldt-Jakob disease (V128) or fatal familial insomnia (M128)(Goldfarb,.Science. 1992). Analysis of Prion with MnM predicts 39 potential functional motifs in Prion protein. Six such motifs were already experimentally confirmed and five motifs were closely related to known effects of Prion and are consistent with published experiments. Painting potential functions onto the surface of Prion protein (Fig. 1) provides an example of how MnM can be used for predicting new functions in proteins and generating new hypotheses for how mutations cause disease. In this case, the 128V variant that favors Creutzfeldt-Jakob disease eliminates a potential Vav2 SH2 binding motif (yellow) that is present in the 128M variant that favors Fatal familial insomnia. Also, the D178N disease associated mutation eliminates a potential Caspase 1 cleavage site (cyan). The Caspase apoptotic cascade is activated by Prion. Several other motifs (N-glycosylation, Grb2-SH2 binding, predicted by MnM surround these important mutations and may be responsive to mutation and/or allelic variation. Several motifs predicted on the opposing face of the protein or on fragments of Prion not shown in this structure are not shown.

Motifs Found in PRION Protein from those found in the Proteomes of the Species HOMO SAPIENS, HUMAN, MAN
Subcellular Localization chosen for search : ALL
Highlighted Motif Known Motif Expected Count In Proteome Observed Count In Proteome Enrichment Factor In Proteome Annotation Occurrence Positions References
1DRY102614311.395"Motif in Melanocortin receptors and G- protein receptors for control of receptor activation, located in cytoplasmic loop "147
2F???W??-I/L/V131615821.202MDM2 binding motif on p5312
3G?G??G4425127612.884"Phosphate, FAD, NADH, binding motif"40, 53, 88 ;
4G>122212221.0Amidation motif (must be in secretory pathway)253
5D/N-?Y??-D/E362942611.174"cCBl TKB domain binding motif, Tyr must be PO4"147
6L???-L/I/V/F/M-??L?-L/I/V7292109351.5Nuclear export signal4, 243
7WM393443721.111Substrate binding motif of barley alpha-amylase 1 (AMY1) enzyme7
8Y??Q17963175740.978SH2 ligand for Stat338, 49, 157, 169
9P?V?L551446470.843Shadow-Chromo domain binding motif238
10Y?N13428158261.179"SH2 ligand group 1B (Abl,Grb2) (needs to be Tyr phosphorylated)(phospho-peptide)"157, 169;[ta]+AND+9[vol]+AND+2827[page]&doptcmdl=Abstract
11L???-L/I/V/F/M-???L?-L/I/V727797081.334Nuclear export signal242
12L??-L/I/V/F/M-???L?-L/I/V7292109201.498Nuclear export signal243
13I/V/L-Y??-P/F762876541.003ABL phosphorylation site161
14Y??M808983651.034SH2 ligand group 3 (P85-PI3K)(phospho-peptide)163
15YM812176180.938SH2 ligand group 2 (Vav) (phospho-peptide)128
16F??????-I/L-I/L10401130381.254ER export motif for G-protein coupled receptors235
17K-K/R-?-K/R10827206981.912Nuclear localization motif24
18F/W/Y/L-?-H/A/T-D-A/C/F/G/H/I/L/M/N/S/T/V/W/Y11633105660.908Protease Caspase 1 from peptide cutter site175
19I/L/V-??Y?-L/V11996122561.022Tyr phosphorylation motif125http://www/
20YE26647244150.916TPK-IIB/P38Syk kinase phosphorylation site (peptide screen)145, 218
21T??D36370366911.009"FHA1 binding motif, Thr must be phosphorylated, binding motif of proteins binding to Chk2"15, 199
22T?Y20192195700.969MEK phosphorylation of MAPK activation site216
23Y??P24372215740.885SH2 ligand group 3 (PLCgamma1 C-term.)(phospho-peptide)162
24S/T-Q94642903580.955ATM kinase phosphorylation site97, 216, 222
25N?-T/S70470793521.126N-linked glycosylation site181, 197
26F?E36865347930.944Motif that recognizes unpaired thymidine in DNA198
27S/T-??E1392891367910.982Casien kinase II consensus phosphorylation site143, 193, 216
28R?-S/T1148971046500.911PKA consensus phosphorylation site220, 228
29P??P605211047421.731"SH3 general ligand,"102
30P?P606401043211.72SH3 binding motif in Pak (nonconventional)26
31Y??-I/L/M61608639381.038SH2 ligand group 3 (Shc)(phospho-peptide)163
32S/T-P1284081429771.113ERK phosphorylation site-general43, 237
33K/R-??-S/T2271592207320.972RSK phosphorylation motif104, 185, 228
34K/R-R967491151441.19Protease Kexin2 cleavage site24
35S??S1001731300881.299"Casien kinase I phosphorylation site, 1st Ser must be phosphorylated"132
36S/T-?-K/R2276092079990.914PKC phosphorylation motif183, 192
37R??-S/T1146701142750.997CamKII consensus phosphorylation site228
38T??-S/A1193041214541.018"FHA of KAPP binding motif, Thr must be phosphorylated"33
39S??-S/T1645511986031.207Casein Kinase I consensus phosphorylation site (N-term Ser must first be phosphorylated)132