CaM-like EF-Hand family of proteins


            There have been several hundred different calcium-binding proteins identified, most of which share the common EF-Hand calcium-binding motif.  The effects of fluctuations in intracellular Ca2+ concentrations are primarily mediated by the EF-Hand superfamily of calcium-binding proteins.  EF-Hand proteins are classified according to the number and structure of their EF-Hands.  Those proteins that contain two pairs of EF-Hands are in the calmodulin-like family of EF-Hand proteins.  There are sixteen different types of proteins within this family, all of which are represented in the table.  One of these proteins, calcineurin, also appears in the list of Ca2+-CaM binding proteins.  The functions of these proteins are quite diverse, and include:  photoproteins such as the calcium-activated photoprotein Aequorin from jellyfish, the photoreceptor recovery protein GCAP 3, and the photoresponse protein Recoverin; signal transduction proteins such as calmodulin, calcineurin, CABP and CLP; muscle proteins that regulate Ca2+ (myosin essential light chain), or muscle contraction (Troponin C); and those involved in cell growth (Calmyrin), or cytokinesis (cdc4).  Collectively, this family of proteins maintains several essential physiological functions.


P02593 Human calmodulin entry from InterPro


Interpro Entry

Method accession

Graphical match

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What InterPro tells us


            The entry for calmodulin shows five signatures for this EF-Hand protein family [IPR002048].  The different proteins used in constructing these signatures are shown in the table.  The PD000012 EF-hand signature from the ProDom database was obtained from an alignment of twelve EF-Hand proteins.  The two bands of the signature reveal information about the domain architecture of calmodulin, which consists of two globular domains (each containing a pair of EF-Hands).  This signature was derived from domain-conserved sequences.

            The PF00036 efhand signature from the PFAM database was obtained from an alignment of 942 EF-Hand protein sequences from several species.  The four bands represent the four EF-Hands (two in each domain) that make up this protein.  This signature was derived from EF-Hand conserved sequences.

            The PS00018 EF_HAND signature from Prosite that was derived from a pattern of conserved sequences reveals the distribution of EF-Hands within the protein, while the Prosite PS50222 EF_HAND_2 signature derived from a matrix reveals the domain architecture.

            The SM00054 Efh signature from the SMART database was obtained from an alignment of 212 EF-Hand protein sequences, including calmodulin.  The signature was derived from EF-Hand conserved sequences.

            The last two entries in the table are from the structural classification databases CATH (1cdlA1) and SCOP (d1a29_), the names being derived from the PDB entries that they describe (for example, d1a29_ is from PDB entry 1a29).  CATH reveals only one of the two domains, while SCOP shows both.  These last two entries were automatically generated, which is the reason they do not have InterPro entries associated with them.

            The different signatures are useful to gain insight into the annotation of the protein and to discern relationships with other proteins or domains within InterPro.  From the InterPro entry you can find all the corresponding proteins in UniProt, a graphical representation of their overlap, the taxonomy of the entries, and any links to other families or domains in the database.


  What the structure tells us


            A description and visualisation of the structural features of calmodulin can be found at the PDB database.  Here you can see the EF-Hand structure of calmodulin and how it relates to its ability to regulate CaM binding proteins.



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