Summary
Src homology-3 domain
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 47 families and the total number of domains in the clan is 267529. The clan was built by RD Finn.
Literature references
- 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 47 member families:
CAP_GLY DUF150_C DUF1541 DUF1653 DUF2642 DUF3104 DUF3148 DUF3247 DUF3601 DUF4222 DUF4314 DUF4453 DUF4926 DUF5397 DUF5776 DUF951 Gemin7 GW hSH3 IN_DBD_C KapB MLVIN_C MSSS Myosin_N NdhS NifZ SH3_1 SH3_10 SH3_11 SH3_12 SH3_13 SH3_14 SH3_15 SH3_16 SH3_17 SH3_18 SH3_19 SH3_2 SH3_3 SH3_4 SH3_5 SH3_6 SH3_9 SlpA Spore_GerQ Vexin YjdMExternal database links
| CATH: | 2.30.30.40 |
| SCOP: | 50044 |
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) | 92969 (34.8%) | View |
| SH3_9 (PF14604) | 52649 (19.7%) | View |
| SH3_2 (PF07653) | 31673 (11.8%) | View |
| CAP_GLY (PF01302) | 17056 (6.4%) | View |
| SH3_3 (PF08239) | 13908 (5.2%) | View |
| Myosin_N (PF02736) | 11655 (4.4%) | View |
| DUF150_C (PF17384) | 6192 (2.3%) | View |
| SH3_10 (PF17902) | 5732 (2.1%) | View |
| SH3_15 (PF18346) | 4762 (1.8%) | View |
| YjdM (PF03831) | 3456 (1.3%) | View |
| SH3_4 (PF06347) | 3367 (1.3%) | View |
| SH3_13 (PF18335) | 2819 (1.1%) | View |
| MSSS (PF20297) | 2682 (1.0%) | View |
| SH3_16 (PF18348) | 2084 (0.8%) | View |
| DUF951 (PF06107) | 1641 (0.6%) | View |
| SH3_12 (PF18129) | 1570 (0.6%) | View |
| DUF1653 (PF07866) | 1448 (0.5%) | View |
| hSH3 (PF14603) | 1273 (0.5%) | View |
| GW (PF13457) | 1083 (0.4%) | View |
| MLVIN_C (PF18697) | 1050 (0.4%) | View |
| IN_DBD_C (PF00552) | 972 (0.4%) | View |
| DUF1541 (PF07563) | 826 (0.3%) | View |
| SlpA (PF03217) | 569 (0.2%) | View |
| NifZ (PF04319) | 567 (0.2%) | View |
| continued | ||
| Pfam family | Num. domains | Alignment |
|---|---|---|
| SH3_19 (PF18597) | 567 (0.2%) | View |
| SH3_5 (PF08460) | 512 (0.2%) | View |
| Spore_GerQ (PF09671) | 508 (0.2%) | View |
| DUF4926 (PF16277) | 489 (0.2%) | View |
| DUF4314 (PF14192) | 489 (0.2%) | View |
| Gemin7 (PF11095) | 434 (0.2%) | View |
| SH3_6 (PF12913) | 399 (0.1%) | View |
| DUF5776 (PF19087) | 375 (0.1%) | View |
| DUF3148 (PF11347) | 340 (0.1%) | View |
| NdhS (PF11623) | 314 (0.1%) | View |
| KapB (PF08810) | 310 (0.1%) | View |
| DUF2642 (PF10842) | 300 (0.1%) | View |
| Vexin (PF15505) | 168 (0.1%) | View |
| DUF4222 (PF13973) | 65 (0.0%) | View |
| DUF3247 (PF11607) | 54 (0.0%) | View |
| DUF5397 (PF17375) | 41 (0.0%) | View |
| SH3_14 (PF18343) | 39 (0.0%) | View |
| DUF4453 (PF14627) | 38 (0.0%) | View |
| DUF3104 (PF11302) | 34 (0.0%) | View |
| DUF3601 (PF12208) | 24 (0.0%) | View |
| SH3_11 (PF18103) | 13 (0.0%) | View |
| SH3_18 (PF18354) | 10 (0.0%) | View |
| SH3_17 (PF18350) | 3 (0.0%) | View |
| Total: 47 | Total: 267529 |
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Family relationships
This diagram shows the relationships between members of this clan. More...
Species distribution
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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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