EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3)
TICN3, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 3 (Spock3), is a brain-specific heparan sulfate proteoglycan that shows a widespread distribution within the extracellular matrix of the brain. It plays an important role in the formation or maintenance of major neuronal structures in the brain. It also functions as a novel regulator to reduce the activity of matrix metalloproteinase (MMP) in adult T-cell leukemia (ATL). It suppresses membrane-type 1 MMP-mediated MMP-2 activation and tumor invasion. Moreover, TICN3 corresponding gene SPOCK3 acts as a risk gene for adult attention-deficit/hyperactivity disorder (ADHD) and personality disorders. TICN3 contains an N-terminal signal peptide, a testican-specific domain followed by the follistatin-like (FS) and extracellular calcium-binding (EC) domains characteristic of the BM-40 family. Towards the C-terminus they contain a thyroglobulin-like domain (TY) and a novel sequence (domain V), which includes two potential glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr295 in the +Y position of EF-hand 2 in testican-3 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.
Feature 1:putative Ca binding site [ion binding site]
Evidence:
Comment:Based on the structure evidence how the first EF-hand motif in Homo sapiens SPARC (1SRA) binds Ca2+ ion.
Comment:Unlike other members in SPARC family, the substitution of a ligating Asp residue by Tyr295 in the +Y position of EF hand 2 in testican-3 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ with low affinity.
Jiyao W et al.(2023). "The conserved domain database in 2023.",