我們這研究提出了模組家族以及跨物種模組交互作用網路的新概念，並將此概念藉 由網站的呈現讓使用者便於查詢及使用，同源網路模組家族網站透過同源模組去定義出 模組之間的交互作用和模組交互作用網路，且此網站服務是第一個提供鄰近模組和藉由 跨物種的模組交互作用網路去觀察各個模組交互作用之間的差異性，以及使用者所查詢 的模組家族中所有物種的蛋白質與蛋白質蛋白質交互作用的所有資訊，並且會使用 GO terms 為所查詢的模組家族和鄰近的模組作註解。
從我們第三節的結果與討論中，我們證明了這網站服務，讓使用者輸入欲查詢的蛋 白質序列或者是基因名稱，此網站服務能提供此蛋白質有出現在哪個模組中，且提供可 視化的跨多個脊椎動物的模組交互作用網路，並且使用模組家族和鄰近的模組來為使用 者所查詢的蛋白質加以註解。
我們相信同源網路模組家族網站可以提供一個快速搜尋同源模組和模組交互作用 的服務，並且能夠為模組演化和細胞生化過程提供有價值的新見解。
39
表二、JAK2-PAFR-TYK2 模組的鄰近模組功能註解 Functional
groups
Module
ID Name
p-value of
MMI
Module family annotation
Module family
annotation at level 5 FunCat annotations [54]
cellular protein metabolic pathway
2563 FGFR2-c-Cbl-Lyn-Fyn complex 2.28E-08 protein phosphorylation
cellular protein metabolic process
(GO: 0044267)
proteasomal degradation (ubiquitin/proteasomal pathway);
tyrosine kinase;
FGF-receptor signalling pathway;
structural cell of tissue (fibroblast, osteoblast, etc.)
cellular protein
metabolic pathway 2564
p21(ras)GAP-Fyn-Lyn-Yes complex, thrombin stimulated
2.28E-08 protein phosphorylation
cellular protein metabolic process
(GO: 0044267)
enzyme mediated signal transduction;
blood coagulation;
platelet cellular protein
metabolic pathway 2565
CD20-LCK-LYN-FYN-p75/80 complex, (Raji human B cell line)
2.28E-08 protein phosphorylation
cellular protein metabolic process
(GO: 0044267)
tyrosine kinase;
B-cell
cellular protein metabolic pathway
1185
EGFR-containing signaling complex
3.99E-05
protein phosphorylation;
cell communication;
phosphoinositide-mediated signaling
cellular protein metabolic process
(GO: 0044267)
EGF-receptor signalling pathway
cell surface receptor linked signaling pathway
5713
SH3P2/OSTF1-CBL-SRC complex
1.06E-05
epidermal growth factor receptor signaling pathway
cell surface receptor linked signaling pathway (GO:
0007166)
cell adhesion;
actin cytoskeleton
40
Module family annotation
Module family
annotation at level 5 FunCat annotations [54]
cell surface receptor linked signaling pathway
1222 Irs1-Grb2-Ptpn1 complex 2.17E-09
insulin receptor signaling pathway
cell surface receptor linked signaling pathway (GO: 0007166)
modification by phosphorylation, dephosphorylation,
autophosphorylation;
insulin receptor signalling pathway cell surface receptor
linked signaling pathway
2577
Sam68-p85 P13K-IRS-1-IR signaling complex
3.77E-12
insulin receptor signaling pathway
cell surface receptor linked signaling pathway (GO: 0007166)
insulin receptor signalling pathway;
cytoplasm
cell surface receptor linked signaling pathway
2535
SLP-76-Cbl-Grb2-Shc complex, Fc receptor gamma-R1 stimulated
2.28E-08
epidermal growth factor receptor signaling pathway
cell surface receptor linked signaling pathway (GO: 0007166)
transmembrane receptor protein tyrosine kinase signalling pathways;
immune response cell surface receptor
linked signaling pathway
2550
Frs2-Grb2-Shp2 complex, FGF stimulated
1.06E-05
fibroblast growth factor receptor signaling pathway
cell surface receptor linked signaling pathway (GO: 0007166)
FGF-receptor signalling pathway
cell surface receptor linked signaling pathway
5282 CAS-SRC-FAK complex 1.06E-05
epidermal growth factor receptor signaling pathway;
nerve growth factor receptor signaling pathway;
integrin-mediated signaling pathway
cell surface receptor linked signaling pathway (GO: 0007166)
transmembrane receptor protein tyrosine kinase signalling pathways
41
表二、JAK2-PAFR-TYK2 模組的鄰近模組功能註解(3) Functional
groups
Module
ID Name
p-value of
MMI
Module family annotation
Module family
annotation at level 5 FunCat annotations [54]
cell surface receptor linked signaling pathway
3096
ITGA6-ITGB4-SHC1-GRB2 complex
3.99E-05
integrin-mediated signaling pathway
cell surface receptor linked signaling pathway (GO: 0007166)
non-enzymatic receptor mediated signalling;
cytoskeleton/structural proteins;
epithelium;
skin
cell surface receptor linked signaling pathway
2529
LAT-PLC-gamma-1-p85-GRB2-CBL-VAV-SLP-76 signaling complex, C305 activated
7.20E-13
T cell receptor signaling pathway;
platelet activation;
nerve growth factor receptor signaling pathway;
T cell costimulation
cell surface receptor linked signaling pathway (GO: 0007166)
polyphosphoinositol mediated signal transduction;
transmembrane receptor protein tyrosine kinase signalling pathways;
adaptive cell mediated response (T-cells)
cell surface receptor linked signaling pathway
2454
CIN85-CBL-SH3GL2-EGFR complex, EGF stimulated
1.06E-05 - -
vesicle formation;
endocytosis
EGF-receptor signalling pathway
cell surface receptor linked signaling pathway
482
cRET-Shc-Grb2-Gab2-P85PI3K-Shp2 complex
3.03E-10 - -
second messenger mediated signal transduction;
transmembrane receptor protein tyrosine kinase signaling pathway
42
Module family annotation
Module family
annotation at level 5 FunCat annotations [54]
cell surface receptor linked signaling pathway
2480
CIN85 complex (CIN85, CRK, BCAR1, CBL, PIK3R1, GRB2, SOS1)
1.35E-09 - -
transmembrane receptor protein tyrosine kinase signalling pathways
cell surface receptor linked signaling pathway
2536
PLC-gamma-2-SLP-76-Lyn-Grb2 complex
2.28E-08 - -
polyphosphoinositol mediated signal transduction;transmembrane receptor protein tyrosine kinase signalling pathways;
blood coagulation;
platelet interleukine receptor
signalling pathway
1515 IL4-IL4R-IL2RG complex 1.06E-05 immune response -
interleukine receptor signalling pathway
interleukine receptor signalling pathway
5564 LMO4-gp130 complex 4.68E-11 - -
transcription activation;
interleukine receptor signalling pathway
interleukine receptor signalling pathway
3203
Shc-Ship-Grb2 complex, IL-3 stimulated
1.06E-05 - -
interleukine receptor signalling pathway
interleukine receptor signalling pathway
1p9m
Crystal structure of the hexameric human IL-6/IL-6 alpha
receptor/gp130 complex
1.06E-05 - - -
43
表二、JAK2-PAFR-TYK2 模組的鄰近模組功能註解(5) Functional
groups
Module
ID Name
p-value of
MMI
Module family annotation
Module family
annotation at level 5 FunCat annotations [54]
2528 ERBB2-MEMO-SHC complex 1.06E-05 - -
cell motility;
microtubule cytoskeleton
- 3678
RIN1-STAM2-EGFR complex, EGF stimulated
1.06E-05 - -
protein targeting, sorting and translocation;
endocytosis;
EGF-receptor signalling pathway;
endosome
- 2542 EGFR-CBL-GRB2 complex 2.17E-09 - -
cellular signalling;
endosome
- 2510
ZAP70-CRKL-WIPF1-WAS complex
3.99E-05 - - cellular signalling
- 2475 Cbl-Crkl-Rapgef1 complex 1.06E-05 blood vessel development
vasculature development (GO: 0001944)
integrin receptor signalling pathway;
cell migration
44
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