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1675  structures 8652  species 0  interactions 267529  sequences 7566  architectures

Clan: SH3 (CL0010)


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 47 families and the total number of domains in the clan is 267529. 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


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 YjdM

External database links

Domain organisation

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

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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
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
No alignment ℹ

Please note: Clan alignments can be very large and can cause problems for some browsers. Read the note above before viewing.

Family relationships

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

Species distribution

Tree controls


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



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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