Sequence analysis identifies a ras-associating (RA)-like domain in the N-termini of band 4.1/JEF domains and in the Grb7/10/14 adapter family.
RA (RalGEF/AF6 or Ras-associating) domains are found in a wide variety of proteins, several of which are known to be Ras-GTP effectors. The three dimensional structure of the RA domain has been experimentally determined in Ral-guanine nucleotide exchange factor (Ral-GEF) and found to be similar to that of the Ras-binding domain of c-Raf1, in spite of a very low level of sequence identity. Using various approaches of sequence analysis, including automatic procedures such as BLAST2, profilescan, and hidden Markov models (HMM), as well as the bidimensional hydrophobic cluster analysis (HCA), here we found that a region with a similar structure is also present at the N-terminus of the band 4.1/JEF domain of KIAA0316 (a human cDNA open reading frame) and H09G03.2 (a related protein sequence predicted from C. elegans genome cloning), as well as in a particular class of adapter proteins including Grb7, Grb10, Grb14, MIG-10, and PRP48. Although the structural conservation of this motif does not necessarily imply a conservation of its ability to bind small GTPases of the Ras superfamily, several proteins with a band 4.1/JEF domain and adapters of the Grb7 group have close functional relationships with such small GTPases. Thus, our finding raises the intriguing possibility of a direct interaction between members of these two groups of proteins and Ras-like GTP-binding proteins.
Wojcik
J
J
Systèmes moléculaires & Biologie structurale, LMCP, CNRS UMR 7590, Universités Paris 6 et Paris 7, case 115, 4 place Jussieu, Paris Cedex 05, 75252, France.
Girault
J A
JA
Labesse
G
G
Chomilier
J
J
Mornon
J P
JP
Callebaut
I
I
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D016208:Databases, Factual; D051383:GRB10 Adaptor Protein; D051382:GRB7 Adaptor Protein; D015801:Helminth Proteins / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009479:Neuropeptides; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D017421:Sequence Analysis; D018631:ras Proteins / Q000737:chemistry*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C099655:GRB14 protein, human; C495955:GRB7 protein, human; D015801:Helminth Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D011506:Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D051382:GRB7 Adaptor Protein; D051383:GRB10 Adaptor Protein; D018631:ras Proteins