The recently reported NIβ domain is already known as the Calx-β motif

May and Ponting1xMay, A.P. and Ponting, C.P. Trends Biochem. Sci. 1999; 24: 12–13Abstract | Full Text | Full Text PDF | PubMed | Scopus (15)See all References1 recently described homologies between integrin-α-subunit and -β-subunit domains and cyanobacterial proteins. However, their analysis of integrin-β homologies reports findings that we published 16 months earlier2xSchwarz, E.M. and Benzer, S. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 10249–10254Crossref | PubMed | Scopus (153)See all References2. Before discussing this, we wish to make clear that this recapitulation of our work was not the sole focus of their article: their demonstration that integrin-α and -β domains coexist in a single bacterial polypeptide remains novel and interesting.We discovered a motif, the Calx-β motif, that is present as a tandem repeat in the cytoplasmic domains of mammalian 3Na+/1Ca2+ exchangers (NCX1, etc.) and of their invertebrate orthologs (CALX, C10G8.5, etc.). The Calx-β motif is also present in the cytoplasmic tail of mammalian integrin β4 and in three functionally uncharacterized Synechocystis sp. PCC6803 proteins (slr0408, slr1028 and slr1403). The Calx-β motif overlaps domains used by NCX1 for calcium binding and regulation. Our analysis of the Calx-β motif, using the PHD neural network, indicated that it contains a series of β-strands and turns, which is consistent with the Calx-β motif forming a self-contained β-sheet.May and Ponting renamed this motif NIβ, despite citing us (indirectly): in their article, the authors state that ‘the NCX tandem repeats…have been reported, but, to our knowledge, documentation of this domain family and the presence of an NIβ domain in the integrin β4 subunit were not appreciated previously.’ Their reference for this statement3xNicoll, D.A. et al. J. Biol. Chem. 1996; 271: 24914–24921Crossref | PubMed | Scopus (261)See all References3, which was published in 1996, cites our finding as a ‘personal communication’. Given our names, a PubMed search would have found our subsequent publication.May and Ponting speculate that ‘a Ca2+-binding role for the β4 NIβ domain would be consistent with the observation that the cytoplasmic region of β4 is cleaved in a Ca2+-dependent manner by calpain and with the proposal that this cleavage plays a role in initiating differentiation of epidermal cells.’ This is an exciting point, citing work that we were not aware of when writing our analysis. However, at least one 3Na+/1Ca2+ exchanger binds ankyrin4xLi, Z.P. et al. J. Biol. Chem. 1993; 268: 11489–11491PubMedSee all References4 and the Calx-β motifs of NCX1 overlap a region needed for inhibition by elevated levels of intracellular Na+ (Ref. 5xMatsuoka, S. et al. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 3870–3874Crossref | PubMedSee all ReferencesRef. 5). It is thus not clear, from sequence comparisons alone, what function the Calx-β motif has. Our discussion of the function of this motif was agnostic on this issue, and we think that several different hypotheses of Calx-β function will require experimental tests.We request that our term Calx-β, and our analysis, be given priority in future literature concerning this fascinating and enigmatic protein domain.