Since the delineation of the EF-hand motif in 1973, the family of EF-hand proteins has expanded to include at least 66 subfamilies thus far.
EF-hand motifs are divided into two major groups:
Canonical EF-hands as seen in calmodulin (CaM) and the prokaryotic CaM-like protein calerythrin.
The 12-residue canonical EF-hand loop binds Ca²⁺ mainly via sidechain carboxylates or carbonyls (loop sequence positions 1, 3, 5, 12).
The residue at the –X axis coordinates the Ca²⁺ ion through a bridged water molecule.
The EF-hand loop has a bidentate ligand (Glu or Asp) at axis –Z.
Pseudo EF-hands exclusively found in the N-termini of S100 and S100-like proteins.
The 14-residue pseudo EF-hand loop chelates Ca²⁺ primarily via backbone carbonyls (positions 1, 4, 6, 9).

Additional points:
EF-hand-like proteins with diversified flanking structural elements around the Ca²⁺-binding loop have been reported in bacteria and viruses.
These prokaryotic EF-hand-like proteins are widely implicated in Ca²⁺ signaling and homeostasis in bacteria.
They contain flexible lengths of Ca²⁺-binding loops that differ from the EF-hand motifs.
However, their coordination properties resemble classical EF-hand motifs.

For example, the semi-continuous Ca²⁺-binding site in D-galactose-binding protein (GBP) contains a nine-residue loop.
The Ca²⁺ ion is coordinated by seven protein oxygen atoms, five of which are from the loop mimicking the canonical EF-loop whereas the other two are from the carboxylate group of a distant Glu.

Another example is a novel domain named Excalibur (extracellular Ca²⁺-binding region) isolated from Bacillus subtilis.
This domain has a conserved 10-residue Ca²⁺-binding loop strikingly similar to the canonical 12-residue EF-hand loop.

The diversity of the structure of the flanking region is illustrated by the discovery of EF-hand-like domains in bacterial proteins.
For example, a helix-loop-strand instead of the helix-loop-helix structure is in periplasmic galactose-binding protein (Salmonella typhimurium, PDB: 1gcg​) or alginate-binding protein (Sphingomonas sp.,
1kwh​); the entering helix is missing in protective antigen (Bacillus anthracis, 1acc​) or dockerin (Clostridium thermocellum, 1daq​).

Among all the structures reported to date, the majority of EF-hand motifs are paired either between two canonical or one pseudo and one canonical motifs.
For proteins with odd numbers of EF-hands, such as the penta-EF-hand calpain, EF-hand motifs were coupled through homo- or hetero-dimerization.
The recently-identified EF-hand containing ER Ca²⁺ sensor protein, stromal interaction molecule 1 and 2 (STIM1, STIM2), has been shown to contain a Ca²⁺-binding canonical EF-hand motif that pairs with an immediate, downstream atypical "hidden" non-Ca²⁺-binding EF-hand.
Single EF-hand motifs can serve as protein-docking modules: for example, the single EF hand in the NKD1 and NKD2 proteins binds the Dishevelled (DVL1, DVL2, DVL3) proteins.

Functionally, the EF-hands can be divided into two classes: 1) signaling proteins and 2) buffering/transport  proteins.
 The first group is the largest and includes the most well-known members of the  family such as calmodulin, troponin C and S100B.  These proteins typically undergo a calcium-dependent conformational change which opens a target binding site.
The latter group is represented by calbindin D9k and do not undergo  calcium dependent conformational changes.
Since the delineation of the EF-hand motif in 1973, the family of EF-hand proteins has expanded to include at least 66 subfamilies thus far. EF-hand motifs are divided into two major groups:
Canonical EF-hands as seen in calmodulin (CaM) and the prokaryotic CaM-like protein calerythrin. The 12-residue canonical EF-hand loop binds Ca²⁺ mainly via sidechain carboxylates or carbonyls (loop sequence positions 1, 3, 5, 12). The residue at the –X axis coordinates the Ca²⁺ ion through a bridged water molecule. The EF-hand loop has a bidentate ligand (Glu or Asp) at axis –Z.
Pseudo EF-hands exclusively found in the N-termini of S100 and S100-like proteins. The 14-residue pseudo EF-hand loop chelates Ca²⁺ primarily via backbone carbonyls (positions 1, 4, 6, 9).
Additional points:
EF-hand-like proteins with diversified flanking structural elements around the Ca²⁺-binding loop have been reported in bacteria and viruses. These prokaryotic EF-hand-like proteins are widely implicated in Ca²⁺ signaling and homeostasis in bacteria. They contain flexible lengths of Ca²⁺-binding loops that differ from the EF-hand motifs. However, their coordination properties resemble classical EF-hand motifs.
For example, the semi-continuous Ca²⁺-binding site in D-galactose-binding protein (GBP) contains a nine-residue loop. The Ca²⁺ ion is coordinated by seven protein oxygen atoms, five of which are from the loop mimicking the canonical EF-loop whereas the other two are from the carboxylate group of a distant Glu.
Another example is a novel domain named Excalibur (extracellular Ca²⁺-binding region) isolated from Bacillus subtilis. This domain has a conserved 10-residue Ca²⁺-binding loop strikingly similar to the canonical 12-residue EF-hand loop.
The diversity of the structure of the flanking region is illustrated by the discovery of EF-hand-like domains in bacterial proteins. For example, a helix-loop-strand instead of the helix-loop-helix structure is in periplasmic galactose-binding protein (Salmonella typhimurium, PDB: 1gcg​) or alginate-binding protein (Sphingomonas sp., 1kwh​); the entering helix is missing in protective antigen (Bacillus anthracis, 1acc​) or dockerin (Clostridium thermocellum, 1daq​).
Among all the structures reported to date, the majority of EF-hand motifs are paired either between two canonical or one pseudo and one canonical motifs. For proteins with odd numbers of EF-hands, such as the penta-EF-hand calpain, EF-hand motifs were coupled through homo- or hetero-dimerization. The recently-identified EF-hand containing ER Ca²⁺ sensor protein, stromal interaction molecule 1 and 2 (STIM1, STIM2), has been shown to contain a Ca²⁺-binding canonical EF-hand motif that pairs with an immediate, downstream atypical "hidden" non-Ca²⁺-binding EF-hand. Single EF-hand motifs can serve as protein-docking modules: for example, the single EF hand in the NKD1 and NKD2 proteins binds the Dishevelled (DVL1, DVL2, DVL3) proteins.
Functionally, the EF-hands can be divided into two classes: 1) signaling proteins and 2) buffering/transport  proteins.  The first group is the largest and includes the most well-known members of the  family such as calmodulin, troponin C and S100B.  These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo  calcium dependent conformational changes.
EF hand