{PDOC50002} {PS50002; SH3} {BEGIN} *************************************** * 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 beta- strands arranged as two tightly packed anti-parallel beta 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-gamma-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 ). 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 beta (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 alpha-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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: October 2017 / Text and profile revised. [ 1] Mayer B.J., Hamaguchi M., Hanafusa H. "A novel viral oncogene with structural similarity to phospholipase C." Nature 332:272-275(1988). PubMed=2450282; DOI=10.1038/332272a0 [ 2] Musacchio A., Gibson T., Lehto V.P., Saraste M. "SH3--an abundant protein domain in search of a function." FEBS Lett. 307:55-61(1992). PubMed=1639195 [ 3] Pawson T., Schlessingert J. "SH2 and SH3 domains." Curr. Biol. 3:434-442(1993). PubMed=15335710 [ 4] Mayer B.J., Baltimore D. "Signalling through SH2 and SH3 domains." Trends Cell Biol. 3:8-13(1993). PubMed=14731533 [ 5] Pawson T. "Protein modules and signalling networks." Nature 373:573-580(1995). PubMed=7531822; DOI=10.1038/373573a0 [ 6] Kuriyan J., Cowburn D. Curr. Opin. Struct. Biol. 3:828-837(1993). [ 7] Morton C.J., Campbell I.D. "SH3 domains. Molecular 'Velcro'." Curr. Biol. 4:615-617(1994). PubMed=7953536 [ 8] Daday C., Kolsek K., Graeter F. "The mechano-sensing role of the unique SH3 insertion in plakin domains revealed by Molecular Dynamics simulations." Sci. Rep. 7:11669-11669(2017). PubMed=28916774; DOI=10.1038/s41598-017-11017-2 [ 9] Abrami L., Dallavilla T., Sandoz P.A., Demir M., Kunz B., Savoglidis G., Hatzimanikatis V., van der Goot F.G. "Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade." Elife 6:0-0(2017). PubMed=28826475; DOI=10.7554/eLife.27826 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}