title: The proline-rich region of glyceraldehyde-3-phosphate dehydrogenase from human sperm may bind SH3 domains, as revealed by a bioinformatic study of low-complexity protein segments.
abstract: Glyceraldehyde-3-phosphate dehydrogenase from human sperm (GAPDHS) provides energy to the sperm flagellum, and is therefore essential for sperm motility and male fertility. This isoform is distinct from somatic GAPDH, not only in being specific for the testis but also because it contains an additional amino-terminal region that encodes a proline-rich motif that is known to bind to the fibrous sheath of the sperm tail. By conducting a large-scale sequence comparison on low-complexity sequences available in databases, we identified a strong similarity between the proline-rich motif from GAPDHS and the proline-rich sequence from Ena/vasodilator-stimulated phosphoprotein-like (EVL), which is known to bind an SH3 domain of dynamin-binding protein (DNMBP). The putative binding partners of the proline-rich GAPDHS motif include SH3 domain-binding protein 4 (SH3BP4) and the IL2-inducible T-cell kinase/tyrosine-protein kinase ITK/TSK (ITK). This result implies that GAPDHS participates in specific signal-transduction pathways. Gene Ontology category-enrichment analysis showed several functional classes shared by both proteins, of which the most interesting ones are related to signal transduction and regulation of hydrolysis. Furthermore, a mutation of one EVL proline to leucine is known to cause colorectal cancer, suggesting that mutation of homologous amino acid residue in the GAPDHS motif may be functionally deleterious.
authors.affiliation: Institute of Computer Science, Polish Academy of Sciences, Warsaw, Poland.|Centre of New Technologies, University of Warsaw, Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Tatjewski
authors.affiliation: Silesian University of Technology, Gliwice, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gruca
authors.affiliation: Centre of New Technologies, University of Warsaw, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Plewczynski
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Grynberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013082:Sperm Tail / Q000201:enzymology*; D018909:src Homology Domains / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; C484449:EVL protein, human; C404497:SH3BP4 protein, human; D011392:Proline; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D007930:Leucine