A human protein-protein interaction network: a resource for annotating the proteome.
Protein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and co-immunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Wnt signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.
Stelzl
Ulrich
U
Max Delbrueck Center for Molecular Medicine, 13092 Berlin-Buch, Germany.
Worm
Uwe
U
Lalowski
Maciej
M
Haenig
Christian
C
Brembeck
Felix H
FH
Goehler
Heike
H
Stroedicke
Martin
M
Zenkner
Martina
M
Schoenherr
Anke
A
Koeppen
Susanne
S
Timm
Jan
J
Mintzlaff
Sascha
S
Abraham
Claudia
C
Bock
Nicole
N
Kietzmann
Silvia
S
Goedde
Astrid
A
Toksöz
Engin
E
Droege
Anja
A
Krobitsch
Sylvia
S
Korn
Bernhard
B
Birchmeier
Walter
W
Lehrach
Hans
H
Wanker
Erich E
EE
D060466:Axin Protein; D019992:Databases as Topic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D040901:Proteomics / Q000379:methods*; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000098855:Collapsin Response Mediator Protein 1
D060466:Axin Protein; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C087425:ANP32A protein, human; C555451:AXIN1 protein, human; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1