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767  structures 1443  species 0  interactions 92969  sequences 2425  architectures

Family: SH3_1 (PF00018)

Summary: SH3 domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "SH3 domain". More...

SH3 domain Edit Wikipedia article

An SH3 domain is a protein module, a characteristic peptide sequence. It is used in signal transduction proteins, often in pathways involving tyrosin kinases. SH3 domains bind to proline-rich sequences (or polyproline helices).

SH3 domains have a consensus sequence:

 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.

SH3 domains are often found in functions concerning the cytoskeleton, the ras protein, and the src kinase. They also increase the substrate specificity of tyrosine kinases by binding far away from the catalytic center of the kinase.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

SH3 domain Provide feedback

SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase P12931. The structure is a partly opened beta barrel.

Literature references

  1. Kami K, Takeya R, Sumimoto H, Kohda D; , EMBO J 2002;21:4268-4276.: Diverse recognition of non-PxxP peptide ligands by the SH3 domains from p67(phox), Grb2 and Pex13p. PUBMED:12169629 EPMC:12169629

Internal database links

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. 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-terminal are packed in close proximity, indicating that they are independent structural modules.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan SH3 (CL0010), which has the following description:

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].

The clan contains the following 47 members:

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


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Representative proteomes UniProt

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: SH3;
Type: Domain
Sequence Ontology: SO:0000417
Author: Cerutti L, Sonnhammer ELL , Eddy SR , Finn RD
Number in seed: 55
Number in full: 92969
Average length of the domain: 47.6 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 6.69 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.9 22.9
Trusted cut-off 22.9 22.9
Noise cut-off 22.8 22.8
Model length: 48
Family (HMM) version: 31
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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_1 domain has been found. There are 767 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044QVZ6 View 3D Structure Click here
A0A044RPG1 View 3D Structure Click here
A0A044RSL2 View 3D Structure Click here
A0A044S3W2 View 3D Structure Click here
A0A044SCT9 View 3D Structure Click here
A0A044SL77 View 3D Structure Click here
A0A044SLN3 View 3D Structure Click here
A0A044SU97 View 3D Structure Click here
A0A044SXD4 View 3D Structure Click here
A0A044T691 View 3D Structure Click here
A0A044TDX5 View 3D Structure Click here
A0A044TM65 View 3D Structure Click here
A0A044TV08 View 3D Structure Click here
A0A044UL68 View 3D Structure Click here
A0A044UU63 View 3D Structure Click here
A0A044UYR4 View 3D Structure Click here
A0A044V9M1 View 3D Structure Click here
A0A044VC58 View 3D Structure Click here
A0A044VJ36 View 3D Structure Click here
A0A077YVI8 View 3D Structure Click here
A0A077YWB6 View 3D Structure Click here
A0A077YWU8 View 3D Structure Click here
A0A077YYP0 View 3D Structure Click here
A0A077YYP8 View 3D Structure Click here
A0A077YYU3 View 3D Structure Click here
A0A077Z042 View 3D Structure Click here
A0A077Z049 View 3D Structure Click here
A0A077Z0Q7 View 3D Structure Click here
A0A077Z473 View 3D Structure Click here
A0A077Z581 View 3D Structure Click here
A0A077Z5F3 View 3D Structure Click here
A0A077Z5Y9 View 3D Structure Click here
A0A077Z690 View 3D Structure Click here
A0A077ZCJ1 View 3D Structure Click here
A0A077ZCW2 View 3D Structure Click here
A0A077ZCY4 View 3D Structure Click here
A0A077ZD04 View 3D Structure Click here
A0A077ZDZ3 View 3D Structure Click here
A0A078BQJ0 View 3D Structure Click here
A0A0A2V255 View 3D Structure Click here