uDENN, DENN, and dDENN: indissociable domains in Rab and MAP kinases signaling pathways.
DENN domains are found in a variety of signaling proteins but their exact function remains undefined. Some of the DENN-containing proteins, such as rat Rab3GEP (Rab3 GDP/GTP exchange protein) or mouse Rab6IP1 (Rab6 interacting protein 1) interact with GTPases of the Rab family. Others, such as human MADD (MAP (Mitogen-activated protein) kinase activating protein containing death domain) and human ST5 (Suppressor of tumoreginicity 5) gene products are involved in regulation of MAPKs (Mitogen-activated protein kinases) signaling pathways. Using a combination of profile-based and bidimensional analyses, we show here that DENN domains are much larger than described to date in domain databases, always encircled on both sides by more divergent domains, that we called uDENN and dDENN. These however share conserved amino acids which could play a key role in the DENN functions.
Levivier
E
E
Systèmes moléculaires & Biologie structurale, LMCP, CNRS UMR 7590, Universités Paris 6 et Paris 7, case 115, 4 place Jussieu, Paris Cedex 05, 75252, France.
Goud
B
B
Souchet
M
M
Calmels
T P
TP
Mornon
J P
JP
Callebaut
I
I
D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D016000:Cluster Analysis; D017124:Conserved Sequence; D016208:Databases, Factual; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004330:Drosophila; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020761:rab1 GTP-Binding Proteins / Q000737:chemistry*
D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; C105852:MADD protein, human; C491371:Madd protein, mouse; C491370:Madd protein, rat; D020761:rab1 GTP-Binding Proteins