Sandbox Reserved 1124: Difference between revisions

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Grb2 (Growth factor receptor-bound protein 2) is a connector protein that link grow factor receptors to the Ras signalling pathway. This protein implied in signal transduction pathways is essential for multiple cellular functions such as: embryonic development, cell proliferation...

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== DNA/RNA ==

The gene which codes the Grb2 protein is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2.

The gene which codes the Grb2 protein is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2. In fact, it is a deletion in the amino-terminal part of the SH2 domain. Therefore, the function is modified because this domain cannot bind the phosphorylated tyrosine.

== Structure ==

Grb2 is a small protein of 217 residues with a molecular ~~size~~ of about 25 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. It has no catalytic domain.

Grb2 is a small protein of 217 residues with a molecular mass of about 25,206 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. It has no catalytic domain.

The central SH2 domain binds growth factor receptors (EGFR or PDGFR) or scaffold proteins. It interacts preferentially with a tyrosine phosphorylated sequence with the following motif: pY-X-N-X (X is a hydrophobic residue).

The two SH3 domains bind proline-rich regions of other proteins and enable the interaction with the Sos protein (guanine nucleotide exchange factor). The N-Terminal SH3 domain plays the main role in this interaction, it binds a proline-rich motif PxxP of the Ct domain of Sos. The Ct SH3 domain improves the overall stability of the Grb2-Sos complex. Moreover, this Ct domain specifically binds to proteins with a P-X-I/L/V-D/N-R-X-X-K-P motif such as Gab1.

Sandbox Reserved 1124: Difference between revisions

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 Grb2 (Growth factor receptor-bound protein 2) is a connector protein that link grow factor receptors to the Ras signalling pathway. This protein implied in signal transduction pathways is essential for multiple cellular functions such as: embryonic development, cell proliferation...
-----
 == DNA/RNA ==
-The gene which codes the Grb2 protein is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2.
+The gene which codes the Grb2 protein is composed of five exons, ranging from 78 to 186 bp, and four introns from 1 to 7 kb. It is transcribed into 2 mRNA arising from alternative splicing. Thus, there are two protein isoforms. The second one does not have the exon of the 3’ coding region, which is the origin of the residues from 59 to 100 in the mature Grb2. In fact, it is a deletion in the amino-terminal part of the SH2 domain. Therefore, the function is modified because this domain cannot bind the phosphorylated tyrosine.
 == Structure ==
-Grb2 is a small protein of 217 residues with a molecular size of about 25 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. It has no catalytic domain.
+Grb2 is a small protein of 217 residues with a molecular mass of about 25,206 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. It has no catalytic domain.
 The central SH2 domain binds growth factor receptors (EGFR or PDGFR) or scaffold proteins. It interacts preferentially with a tyrosine phosphorylated sequence with the following motif: pY-X-N-X (X is a hydrophobic residue).
 The two SH3 domains bind proline-rich regions of other proteins and enable the interaction with the Sos protein (guanine nucleotide exchange factor). The N-Terminal SH3 domain plays the main role in this interaction, it binds a proline-rich motif PxxP of the Ct domain of Sos. The Ct SH3 domain improves the overall stability of the Grb2-Sos complex. Moreover, this Ct domain specifically binds to proteins with a P-X-I/L/V-D/N-R-X-X-K-P motif such as Gab1.