SH3 domain

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SH3 domain
SCOP2
1shf / SCOPe / SUPFAM
CDDcd00174
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

The SRC Homology 3 Domain (or SH3 domain) is a small

signal transduction pathways[6] and regulating the interactions of proteins involved in the cytoplasmic signaling.[7]

Structure

The SH3 domain has a characteristic

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.[8]

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.[9][10] Nevertheless, orthologous SH3 domain-mediated interactions are highly rewired between worm and yeast.[9]

Proteins with SH3 domain

See also

  • Src homology 2 domain-containing
  • Structural domain

References

  1. S2CID 53273571
    .
  2. PMID 11256992
    .
  3. S2CID 8564342
    .
  4. PMID 14731533
    .
  5. S2CID 4324726
    .
  6. PMID 8193536
    .
  7. PMID 1708916
    .
  8. PMID 10322416
    .
  9. ^
    PMID 23549480
    .
  10. PMID 19841731
    .

External links
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