To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https
PROSITE documentation PDOC50002

Src homology 3 (SH3) domain profile


The Src homology 3 (SH3) domain is a small protein domain of about 60 amino-acid residues first identified as a conserved sequence in the non-catalytic part of several cytoplasmic protein tyrosine kinases (e.g. Src, Abl, Lck) [1]. Since then, it has been found in a great variety of other intracellular or membrane-associated proteins [2,3,4,5].

The SH3 domain has a characteristic fold which consists of five or six β-strands arranged as two tightly packed anti-parallel β sheets. The linker regions may contain short helices [6].

The function of the SH3 domain is not well understood. The current opinion is that they mediate assembly of specific protein complexes via binding to proline-rich peptides [7].

In general SH3 domains are found as single copies in a given protein, but there is a significant number of protein with two SH3 domains and a few with 3 or 4 copies.

So far, SH3 domains have been identified in the following proteins:

  • Many vertebrate, invertebrate and retroviral cytoplasmic (non-receptor) protein tyrosine kinases. In particular in the Src, Abl, Bkt, Csk and ZAP70 families of kinases.
  • Mammalian phosphatidylinositol-specific phospholipase C-γ-1 and -2.
  • Mammalian phosphatidyl inositol 3-kinase regulatory p85 subunit.
  • Mammalian Ras GTPase-activating protein (GAP).
  • Adaptor proteins mediating binding of guanine nucleotide exchange factors to growth factor receptors: vertebrate GRB2, Caenorhabditis elegans sem-5 and Drosophila DRK. All of which have two SH3 domains.
  • Mammalian Vav oncoprotein, a guanine nucleotide exchange factor of the CDC24 family.
  • Some guanine-nucleotide releasing factors of the CDC25 family: yeast CDC25, yeast SCD25, fission yeast ste6.
  • MAGUK proteins. These proteins consist of at least three types of domains: one or more copies of the DHR domain, a SH3 domain and a C-terminal guanylate kinase domain (see <PDOC00670>). Members of this family are: Drosophila lethal(1)discs large-1 tumor suppressor protein (gene Dlg1), mammalian tight junction protein ZO-1, vertebrate erythrocyte membrane protein p55, Caenorhabditis elegans protein lin-2, rat protein CASK and mammalian synaptic proteins SAP90/PSD-95, CHAPSYN-110/PSD-93, SAP97/DLG1 and SAP102.
  • Plakin family of proteins, important actors in cross-linking force-bearing structures in the cell, contain a curious SH3 domain insertion in their chain of spectrin repeats [8].
  • Miscellanous proteins interacting with vertebrate receptor protein tyrosine kinases: mammalian cytoplasmic protein Nck (3 copies), oncoprotein Crk (2 copies).
  • Chicken Src substrate p80/85 protein (cortactin) and the similar human hemopoietic lineage cell specific protein Hs1.
  • Mammalian dihydrouridine-sensitive L-type calcium channel β (regulatory) subunit including the related human myasthenic syndrome antigen B (MSYB).
  • Mammalian neutrophil cytosolic activators of NADPH oxidase: p47 (NCF-1), p67 (NCF-2), and a potential homolog from Caenorhabditis elegans (B0303.7). NCF-1 and -2 have two copies of the SH3 domain, while B0303.7 has four.
  • Some myosin heavy chains from amoebas, slime molds and yeast (gene MYO3).
  • Mammalian palmitoyltransferase ZDHHC6 [9].
  • Vertebrate and Drosophila spectrin and fodrin α-chain.
  • Human amphiphysin.
  • Yeast actin-binding protein ABP1.
  • Yeast actin-binding protein SLA1 (3 copies).
  • Yeast protein BEM1 and the fission yeast homolog scd2 (or ral3) (2 copies).
  • Yeast BEM1-binding proteins BOI2 (BEB1) and BOB1 (BOI1).
  • Yeast fusion protein FUS1.
  • Yeast protein RSV167.
  • Yeast protein SSU81.
  • Yeast hypothetical proteins YAR014c (1 copy), YFR024c (1 copy), YHL002w (1 copy), YHR016c (1 copy), YJL020C (1 copy), YHR114w (2 copies) and the fission yeast homolog SpAC12C2.05c.
  • Caenorhabditis elegans hypothetical protein F42H10.3.

The profile we developed covers the entire SH3 domain.

Last update:

October 2017 / Text and profile revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

SH3, PS50002; Src homology 3 (SH3) domain profile  (MATRIX)


1AuthorsMayer B.J., Hamaguchi M., Hanafusa H.
TitleA novel viral oncogene with structural similarity to phospholipase C.
SourceNature 332:272-275(1988).
PubMed ID2450282

2AuthorsMusacchio A., Gibson T., Lehto V.P., Saraste M.
TitleSH3--an abundant protein domain in search of a function.
SourceFEBS Lett. 307:55-61(1992).
PubMed ID1639195

3AuthorsPawson T., Schlessingert J.
TitleSH2 and SH3 domains.
SourceCurr. Biol. 3:434-442(1993).
PubMed ID15335710

4AuthorsMayer B.J., Baltimore D.
TitleSignalling through SH2 and SH3 domains.
SourceTrends Cell Biol. 3:8-13(1993).
PubMed ID14731533

5AuthorsPawson T.
TitleProtein modules and signalling networks.
SourceNature 373:573-580(1995).
PubMed ID7531822

6AuthorsKuriyan J., Cowburn D.
SourceCurr. Opin. Struct. Biol. 3:828-837(1993).

7AuthorsMorton C.J., Campbell I.D.
TitleSH3 domains. Molecular 'Velcro'.
SourceCurr. Biol. 4:615-617(1994).
PubMed ID7953536

8AuthorsDaday C., Kolsek K., Graeter F.
TitleThe mechano-sensing role of the unique SH3 insertion in plakin domains revealed by Molecular Dynamics simulations.
SourceSci. Rep. 7:11669-11669(2017).
PubMed ID28916774

9AuthorsAbrami L., Dallavilla T., Sandoz P.A., Demir M., Kunz B., Savoglidis G., Hatzimanikatis V., van der Goot F.G.
TitleIdentification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade.
SourceElife 6:0-0(2017).
PubMed ID28826475

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)