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564  structures 4044  species 16  interactions 40209  sequences 2030  architectures

Clan: SH3 (CL0010)

Summary

Src homology-3 domain Add an annotation

Src homology-3 (SH3) domains are comprised of about 60 amino acids, performing either an assembly or regulatory role. For example, SH3 domains in the Grb2 adaptor protein are essential for protein-protein interactions and signal transduction in the p21 Ras-dependent growth factor signaling pathway. Alternatively, SH3 performs a regulatory role in the Src family of tyrosine kinases. SH3 domains bind a variety of peptide ligands, many of which contain a PxxP motif. This PxxP motif is flanked by different specificity elements [1]. Structures of SH3 domains, both free and ligand complexed, have provided insights into the mechanism of ligand recognition. The SH3 fold consists of two anti-parallel beta sheets that lie at right angles to each other. Within the fold, there are two variable loops, referred to as RT and n-Src loops. When SH3 binds to its ligand, the proline rich ligand adopts a PPII helix conformation, with the PPII helix structure recognised by a pair of grooves on the surface of the SH3 domain that bind turns of the helix. The SH3 grooves are formed by a series of nearly parallel, well-conserved aromatic residues [1].

This clan contains 9 families and the total number of domains in the clan is 40209. The clan was built by RD Finn.

Literature references

  1. Zarrinpar A, Bhattacharyya RP, Lim WA; , Sci STKE 2003;179:RE8.: The structure and function of proline recognition domains. PUBMED:12709533 EPMC:12709533

Members

This clan contains the following 9 member families:

hSH3 SH3_1 SH3_2 SH3_3 SH3_4 SH3_5 SH3_6 SH3_8 SH3_9

External database links

Domain organisation

Below is a listing of the unique domain organisations or architectures from this clan. More...

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Alignments

The table below shows the number of occurrences of each domain throughout the sequence database. More...

Pfam family Num. domains Alignment
SH3_1 (PF00018) 10749 (26.7%) View
SH3_3 (PF08239) 10209 (25.4%) View
SH3_9 (PF14604) 9839 (24.5%) View
SH3_2 (PF07653) 4617 (11.5%) View
SH3_8 (PF13457) 1627 (4.0%) View
SH3_5 (PF08460) 1610 (4.0%) View
SH3_4 (PF06347) 1011 (2.5%) View
SH3_6 (PF12913) 435 (1.1%) View
hSH3 (PF14603) 112 (0.3%) View
Total: 9 Total: 40209 Clan alignment
 

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Family relationships

This diagram shows the relationships between members of this clan. More...

Species distribution

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This tree shows the occurrence of the domains in this clan across different species. More...

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Interactions

There are 16 interactions for this clan. More...

Interacting families
A B
SH3_1 SH2
SH3_1
Ank
PH
ubiquitin
LIM
PB1
RhoGEF
P53
SH3_2
Pkinase_Tyr
SH3_2 SH2
SH3_1
Guanylate_kin
SH3_2
SH3_5 SH3_5

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD group, to allow us to map Pfam domains onto UniProt three-dimensional structures. The table below shows the mapping between the Pfam families in this clan, the corresponding UniProt entries, and the region of the three-dimensional structures that are available for that sequence.

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