• Source: SH3 domain

The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.




Structure


The SH3 domain has a characteristic beta-barrel fold that consists of five or six β-strands arranged as two tightly packed anti-parallel β sheets. The linker regions may contain short helices. The SH3-type fold is an ancient fold found in eukaryotes as well as prokaryotes.




Peptide binding


The classical SH3 domain is usually found in proteins that interact with other proteins and mediate assembly of specific protein complexes, typically via binding to proline-rich peptides in their respective binding partner. Classical SH3 domains are restricted in humans to intracellular proteins, although the small human MIA family of extracellular proteins also contain a domain with an SH3-like fold.
Many SH3-binding epitopes of proteins have a consensus sequence that can be represented as a regular expression or Short linear motif:

-X-P-p-X-P-
1 2 3 4 5

with 1 and 4 being aliphatic amino acids, 2 and 5 always and 3 sometimes being proline. The sequence binds to the hydrophobic pocket of the SH3 domain. More recently, SH3 domains that bind to a core consensus motif R-x-x-K have been described. Examples are the C-terminal SH3 domains of adaptor proteins like Grb2 and Mona (a.k.a. Gads, Grap2, Grf40, GrpL etc.). Other SH3 binding motifs have emerged and are still emerging in the course of various molecular studies, highlighting the versatility of this domain.




SH3 interactomes


SH3 domain-mediated protein-protein interaction networks, i.e., SH3 interactomes, revealed that worm SH3 interactome resembles the analogous yeast network because it is significantly enriched for proteins with roles in endocytosis. Nevertheless, orthologous SH3 domain-mediated interactions are highly rewired between worm and yeast.




Proteins with SH3 domain


Signal transducing adaptor proteins
CDC24
Cdc25
PI3 kinase
Phospholipase
Ras GTPase-activating protein
Vav proto-oncogene
GRB2
p54 S6 kinase 2 (S6K2)
SH3D21
ARMH3 (potentially)
STAC3
Some myosins
SH3 and multiple ankyrin repeat domains: SHANK1, SHANK2, SHANK3
YAP1
ARHGAP12
vexin (VXN)
TANGO1
Integrase
Focal Adhesion Kinase (FAK, PTK2)
Proline-rich tyrosine kinase (Pyk2, CADTK, PTK2beta)
TRIP10 (cip4)




See also


Src homology 2 domain-containing
Structural domain




References






External links


Eukaryotic Linear Motif resource motif class LIG_SH3_1
Eukaryotic Linear Motif resource motif class LIG_SH3_2
Eukaryotic Linear Motif resource motif class LIG_SH3_3
Eukaryotic Linear Motif resource motif class LIG_SH3_4
Eukaryotic Linear Motif resource motif class LIG_SH3_5
Eukaryotic Linear Motif resource motif class TRG_PEX_1
Nash Lab Protein Interaction Domains in Signal Transduction - The SH3 domain
GENEART - Screen your protein against all human SH3 domains in a single phage display cycle Archived 2009-07-07 at the Wayback Machine

Kata Kunci Pencarian:

• SHANK1
• Protein tau
• BCAR1
• ZAP70
• ELMO2
• Protein Wiskott–Aldrich syndrome
• Teneurin
• BMX (gen)
• Protein
• SH3 domain
• Src family kinase
• GRB2
• ABL (gene)
• GRAP
• SH3
• Proto-oncogene tyrosine-protein kinase Src
• Bruton's tyrosine kinase
• PLCG1
• Protein domain