What is the Difference Between Calbindin Calretinin and Calmodulin

The key difference between calbindin calretinin and calmodulin is that calbindin is a protein involved in calcium binding and absorption, while calretinin is a protein involved in calcium signalling, while calmodulin is a protein that functions as a multifunctional intermediate calcium-binding messenger.

Calcium homeostasis is an important process in a healthy body. It is achieved by the regulation of calcium absorption and removal of excess calcium. Calcium homeostasis is regulated by intestinal calcium absorption, urinal calcium excretion, and bone formation. Calbindin, calretinin, and calmodulin are three important proteins to maintain calcium homeostasis.

CONTENTS

1. Overview and Key Difference
2. What is Calbindin 
3. What is Calretinin
4. What is Calmodulin
5. Similarities – Calbindin Calretinin and Calmodulin
6. Calbindin vs Calretinin vs Calmodulin in Tabular Form
7. Summary – Calbindin vs Calretinin vs Calmodulin

What is Calbindin?

Calbindin is a vitamin D responsive calcium-binding protein involved in calcium absorption. Calbindin depends on vitamin D for calcium absorption. It was found initially in the intestines of birds, and it was later found in mammals. Specifically in mammals, it is present in the kidneys. Other than the kidney, calbindin is present in both neuronal and endocrine cells.

Calbindin protein is encoded by the gene CALB1. Calbindin consists of 4 active calcium-binding domains with 2 modified domains. The modified domains do not have the capacity for calcium-binding. Calbindin also acts as a calcium buffer. At once, calbindin can hold 4 Ca²⁺ in the calbindin structure, which is called the EF-hands of loops. EF-hands of loops are a helix structural domain. Calbindin has 4 EF-hands of loops.

What is Calretinin?

Calretinin is a calcium-binding protein involved in calcium signalling for the calcium binding process. Calretinin protein is encoded by the gene CALB2. Calretinin consists of six EF-hands of loops. Calretinin fulfills diverse cellular functions, including intracellular calcium buffering and message targeting. Unlike calbindin, calretinin is not dependent on vitamin D. Calretinin is mostly present in neurons (mostly in the retina) and cortical interneurons.

Calretinin plays a critical role in the modulation of neuronal excitability, especially in the induction of long-term potentiation. The loss of expression of calretinin in hippocampal interneurons causes temporal lobe epilepsy. Calretinin is also present in hair follicles. The clinical significance of calretinin is that it is used as a diagnostic marker for many cancers and Hirschsprung disease.

What is Calmodulin?

Calmodulin is a modulating protein involved in the calcium-binding process. It is a multifunctional intermediate calcium-binding messenger present in all eukaryotic cells. Activation of calmodulin only occurs in response to the binding of Ca²⁺. Upon binding and activation of calmodulin, it acts as a part of the calcium signalling transduction pathway.

Calmodulin modifies its interactions with various target proteins. These proteins include phosphatases and kinases. Calmodulin consists of 148 amino acids; hence it is a small but highly conserved protein. Unlike calbindin and calretinin, calmodulin possesses two approximately symmetrical globular domains; each domain consists of a pair of EF-hand motifs. Calmodulin has a high level of structural flexibility since it targets a wide range of target proteins.

What are the Similarities Between Calbindin Calretinin and Calmodulin?

• Calbindin, calretinin, and calmodulin are proteins.
• All three are essential in calcium metabolism.
• Moreover, all three proteins consist of Ef hands of loops.
• They are mainly composed of helical proteins.
• They are present in mammals.
• All three types are critical in regulating calcium-binding and absorption.

What is the Difference Between Calbindin Calretinin and Calmodulin?

Calbindin is a protein involved in calcium-binding and absorption, while calretinin is a protein involved in calcium signalling and calmodulin is a protein that functions as a multifunctional intermediate calcium-binding messenger. Thus, this is the key difference between calbindin calretinin and calmodulin. The genes involved in coding calbindin, calretinin, and calmodulin are CALB1, CALB2, and CALM1,2,3, respectively. While calbindin is directly dependent on vitamin D, calretinin is independent of vitamin D. However, the role of vitamin D dependency on calmodulin has not been discovered yet.

The below infographic presents the differences between calbindin calretinin and calmodulin in tabular form for side by side comparison.

Summary – Calbindin vs Calretinin vs Calmodulin

Calbindin, calretinin, and calmodulin are three proteins involved in calcium homeostasis. Calbindin is essential in calcium binding and absorption, while calretinin is essential in calcium signalling during calcium binding, and calmodulin functions as a multifunctional intermediate calcium-binding messenger protein. The genes involved in coding calbindin, calretinin, and calmodulin are CALB1, CALB2, and CALM1,2,3, respectively. So, this summarizes the difference between calbindin calretinin and calmodulin.

Reference:

1. “Calbindin.” Neuromics.
2. “Calmodulin.” An Overview | ScienceDirect Topics.
3. Schwaller, Beat. “Calretinin: From a ‘Simple’ Ca(2+) Buffer to a Multifunctional Protein Implicated in Many Biological Processes.” Frontiers in Neuroanatomy, Frontiers Media S.A..

Image Courtesy:

1. “Calbindin2G9B.pdb” By Jmol creaters – Jmol (FAL) via Commons Wikimedia
2. “Malignant epithelioid mesothelioma – calretinin – intermed mag” By Nephron – Own work (CC BY-SA 3.0) via Commons Wikimedia
3. “Calmodulin Binding sites” By PDB – These images are from the Molecule of the Month feature by David Goodsell at the RCSB Protein Data Bank, (CC BY-SA 4.0) via Commons Wikimedia