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 "147http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15215606
2F???W??-I/L/V131615821.202MDM2 binding motif on p5312http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8875929&dopt=Abstract
3G?G??G4425127612.884"Phosphate, FAD, NADH, binding motif"40, 53, 88http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9538688 ;
4G>122212221.0Amidation motif (must be in secretory pathway)253http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11028916
5D/N-?Y??-D/E362942611.174"cCBl TKB domain binding motif, Tyr must be PO4"147http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15123609
6L???-L/I/V/F/M-??L?-L/I/V7292109351.5Nuclear export signal4, 243http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12520031
7WM393443721.111Substrate binding motif of barley alpha-amylase 1 (AMY1) enzyme7http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12423336
8Y??Q17963175740.978SH2 ligand for Stat338, 49, 157, 169http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14966128&query_hl=9
9P?V?L551446470.843Shadow-Chromo domain binding motif238http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10801440
10Y?N13428158261.179"SH2 ligand group 1B (Abl,Grb2) (needs to be Tyr phosphorylated)(phospho-peptide)"157, 169http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7511210; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&term=Oncogene[ta]+AND+9[vol]+AND+2827[page]&doptcmdl=Abstract
11L???-L/I/V/F/M-???L?-L/I/V727797081.334Nuclear export signal242http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12520031
12L??-L/I/V/F/M-???L?-L/I/V7292109201.498Nuclear export signal243http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12520031
13I/V/L-Y??-P/F762876541.003ABL phosphorylation site161http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14757045
14Y??M808983651.034SH2 ligand group 3 (P85-PI3K)(phospho-peptide)163http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7511210
15YM812176180.938SH2 ligand group 2 (Vav) (phospho-peptide)128http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7511210
16F??????-I/L-I/L10401130381.254ER export motif for G-protein coupled receptors235http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15123661
17K-K/R-?-K/R10827206981.912Nuclear localization motif24http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11796712&dopt=Abstract
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 site175http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10872455&dopt=Abstract
19I/L/V-??Y?-L/V11996122561.022Tyr phosphorylation motif125http://www/ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14709333
20YE26647244150.916TPK-IIB/P38Syk kinase phosphorylation site (peptide screen)145, 218http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11286893
21T??D36370366911.009"FHA1 binding motif, Thr must be phosphorylated, binding motif of proteins binding to Chk2"15, 199http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12702867
22T?Y20192195700.969MEK phosphorylation of MAPK activation site216http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1849075
23Y??P24372215740.885SH2 ligand group 3 (PLCgamma1 C-term.)(phospho-peptide)162http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7511210
24S/T-Q94642903580.955ATM kinase phosphorylation site97, 216, 222http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10608806
25N?-T/S70470793521.126N-linked glycosylation site181, 197http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3549291
26F?E36865347930.944Motif that recognizes unpaired thymidine in DNA198http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11602569&dopt=Abstract
27S/T-??E1392891367910.982Casien kinase II consensus phosphorylation site143, 193, 216http://www.neb.com/nebecomm/tech_reference/protein_tools/protein_kinase_substrate_recognition.asp
28R?-S/T1148971046500.911PKA consensus phosphorylation site220, 228http://www.neb.com/nebecomm/tech_reference/protein_tools/protein_kinase_substrate_recognition.asp
29P??P605211047421.731"SH3 general ligand,"102http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7855886
30P?P606401043211.72SH3 binding motif in Pak (nonconventional)26http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12676796
31Y??-I/L/M61608639381.038SH2 ligand group 3 (Shc)(phospho-peptide)163http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7511210
32S/T-P1284081429771.113ERK phosphorylation site-general43, 237http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10637505
33K/R-??-S/T2271592207320.972RSK phosphorylation motif104, 185, 228http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12832467
34K/R-R967491151441.19Protease Kexin2 cleavage site24http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2646633&dopt=Abstract
35S??S1001731300881.299"Casien kinase I phosphorylation site, 1st Ser must be phosphorylated"132http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1995625
36S/T-?-K/R2276092079990.914PKC phosphorylation motif183, 192http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2413024
37R??-S/T1146701142750.997CamKII consensus phosphorylation site228http://www.neb.com/nebecomm/tech_reference/protein_tools/protein_kinase_substrate_recognition.asp
38T??-S/A1193041214541.018"FHA of KAPP binding motif, Thr must be phosphorylated"33http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11069759
39S??-S/T1645511986031.207Casein Kinase I consensus phosphorylation site (N-term Ser must first be phosphorylated)132http://www.neb.com/nebecomm/tech_reference/protein_tools/protein_kinase_substrate_recognition.asp