Summary: Variant SH3 domain
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Internal database links
|Similarity to PfamA using HHSearch:||SH3_1 SH3_2 SH3_3 hSH3|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001452
SH3 (src Homology-3) domains are small protein modules containing approximately 50 amino acid residues [PUBMED:15335710, PUBMED:11256992]. They are found in a great variety of intracellular or membrane-associated proteins [PUBMED:1639195, PUBMED:14731533, PUBMED:7531822] for example, in a variety of proteins with enzymatic activity, in adaptor proteins, such as fodrin and yeast actin binding protein ABP-1.
The SH3 domain has a characteristic fold which consists of five or six beta-strands arranged as two tightly packed anti-parallel beta sheets. The linker regions may contain short helices [PUBMED:]. The surface of the SH3-domain bears a flat, hydrophobic ligand-binding pocket which consists of three shallow grooves defined by conservative aromatic residues in which the ligand adopts an extended left-handed helical arrangement. The ligand binds with low affinity but this may be enhanced by multiple interactions. The region bound by the SH3 domain is in all cases proline-rich and contains PXXP as a core-conserved binding motif. The function of the SH3 domain is not well understood but they may mediate many diverse processes such as increasing local concentration of proteins, altering their subcellular location and mediating the assembly of large multiprotein complexes [PUBMED:7953536].
The crystal structure of the SH3 domain of the cytoskeletal protein spectrin, and the solution structures of SH3 domains of phospholipase C (PLC-y) and phosphatidylinositol 3-kinase p85 alpha-subunit, have been determined [PUBMED:1279434, PUBMED:7684655, PUBMED:7681365]. In spite of relatively limited sequence similarity, their overall structures are similar. The domains belong to the alpha+beta structural class, with 5 to 8 beta-strands forming 2 tightly-packed, anti-parallel beta-sheets arranged in a barrel-like structure, and intervening loops sometimes forming helices. Conserved aliphatic and aromatic residues form a hydrophobic core (A11, L23, A29, V34, W42, L52 and V59 in PLC-y [PUBMED:7681365]) and a hydrophobic pocket on the molecular surface (L12, F13, W53 and P55 in PLC-y). The conserved core is believed to stabilise the fold, while the pocket is thought to serve as a binding site for target proteins. Conserved carboxylic amino acids located in the loops, on the periphery of the pocket (D14 and E22), may be involved in protein-protein interactions via proline-rich regions. The N- and C-termini are packed in close proximity, indicating that they are independent structural modules.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||protein binding (GO:0005515)|
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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 . 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 .
The clan contains the following 9 members:hSH3 SH3_1 SH3_2 SH3_3 SH3_4 SH3_5 SH3_6 SH3_8 SH3_9
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Curation and family details
|Seed source:||Jackhmmer, JCSG:target_422527|
|Number in seed:||30|
|Number in full:||12188|
|Average length of the domain:||51.10 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||7.92 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||2|
|Download:||download the raw HMM for this family|
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There are 10 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the SH3_9 domain has been found. There are 110 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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