Calcium-binding protein

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Calcium-binding proteins are proteins that participate in calcium cell signaling pathways by binding to Ca2+, the calcium ion that plays an important role in many cellular processes. Calcium-binding proteins have specific domains that bind to calcium and are known to be heterogeneous.

Contents

One of the functions of calcium binding proteins is to regulate the amount of free (unbound) Ca2+ in the cytosol of the cell. [1] The cellular regulation of calcium is known as calcium homeostasis.

Types

Many different calcium-binding proteins exist, with different cellular and tissue distribution and involvement in specific functions. Calcium binding proteins also serve an important physiological role for cells. [2] The most ubiquitous Ca2+-sensing protein, found in all eukaryotic organisms including yeasts, is calmodulin. Intracellular storage and release of Ca2+ from the sarcoplasmic reticulum is associated with the high-capacity, low-affinity calcium-binding protein calsequestrin. [3] Calretinin is another type of Calcium binding protein weighing 29kD. It is involved in cell signaling and shown to exist in neurons. This type of protein is also found in large quantities in malignant mesothelial cells, which can be easily differentiated from carcinomas. This differentiation is later applied for a diagnosis on ovarian stromal tumors. [4] Also, another member of the EF-hand superfamily is the S100B protein, which regulates p53. P53 is known as a tumor suppressor protein and in this case acts as a transcriptional activator or repressor of numerous genes. S100B proteins are abundantly found in cancerous tumor cells causing them to be overexpressed, therefore making these proteins useful for classifying tumors. In addition, this explains why this protein can easily interact with p53 when transcriptional regulation takes place. [5]

Calcium-binding proteins can be either intracellular and extracellular. Those that are intracellular can contain or lack a structural EF-hand domain. Extracellular calcium-binding proteins are classified into six groups. [2] Since Ca (2+) is an important second messenger, it can act as an activator or inhibitor in gene transcription. Those that belong to the EF-hand superfamily such as Calmodulin and Calcineurin have been linked to transcription regulation. When levels of Ca(2+) increase in the cell, these members of the EF-hand superfamily regulate transcription indirectly by phosphorylating/dephosphorylating transcription factors. [5]

Secretory calcium-binding phosphoprotein

The secretory calcium-binding phosphoprotein (SCPP) gene family consists of an ancient group of genes emerging around the same time as bony fish. SCPP genes are roughly divided into acidic and P/Q-rich types: the former mostly participates in bone and dentin formation, while the latter usually participate in enamel/enameloid formation. In mammals, P/Q-rich SCPP is also found in saliva and milk and includes unorthodox members such as MUC7 (a mucin) and casein. SCPP genes are recognized by exon structure rather than protein sequence. [6]

Functions

With their role in signal transduction, calcium-binding proteins contribute to all aspects of the cell's functioning, from homeostasis to learning and memory. For example, the neuron-specific calexcitin has been found to have an excitatory effect on neurons, and interacts with proteins that control the firing state of neurons, such as the voltage-dependent potassium channel. [7]

Compartmentalization of calcium binding proteins such as calretinin and calbindin-28 kDa has been noted within cells, suggesting that these proteins perform distinct functions in localized calcium signaling. [8] It also indicates that in addition to freely diffusing through the cytoplasm to attain a homogeneous distribution, calcium binding proteins can bind to cellular structures through interactions that are likely important for their functions. [8]

See also

Related Research Articles

<span class="mw-page-title-main">Calmodulin</span> Messenger protein

Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of calmodulin. Once bound to Ca2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases.

<span class="mw-page-title-main">Paracrine signaling</span> Form of localized cell signaling

In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

A hormone receptor is a receptor molecule that binds to a specific hormone. Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other receptors for various ligands, such as fatty acids and prostaglandins. Hormone receptors are of mainly two classes. Receptors for peptide hormones tend to be cell surface receptors built into the plasma membrane of cells and are thus referred to as trans membrane receptors. An example of this is Actrapid. Receptors for steroid hormones are usually found within the protoplasm and are referred to as intracellular or nuclear receptors, such as testosterone. Upon hormone binding, the receptor can initiate multiple signaling pathways, which ultimately leads to changes in the behavior of the target cells.

<span class="mw-page-title-main">CREB</span> Class of proteins

CREB-TF is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.

CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. When activated, the enzymes transfer phosphates from ATP to defined serine or threonine residues in other proteins, so they are serine/threonine-specific protein kinases. Activated CAMK is involved in the phosphorylation of transcription factors and therefore, in the regulation of expression of responding genes. CAMK also works to regulate the cell life cycle (i.e. programmed cell death), rearrangement of the cell's cytoskeletal network, and mechanisms involved in the learning and memory of an organism.

<span class="mw-page-title-main">Calcium signaling</span> Intracellular communication process

Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.

<span class="mw-page-title-main">S100 protein</span> Family of vertebrate proteins involved in cell division and inflammation

The S100 proteins are a family of low molecular-weight proteins found in vertebrates characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand-type") conformation. At least 21 different S100 proteins are known. They are encoded by a family of genes whose symbols use the S100 prefix, for example, S100A1, S100A2, S100A3. They are also considered as damage-associated molecular pattern molecules (DAMPs), and knockdown of aryl hydrocarbon receptor downregulates the expression of S100 proteins in THP-1 cells.

<span class="mw-page-title-main">Calbindin</span> Protein

Calbindins are three different calcium-binding proteins: calbindin, calretinin and S100G. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney of chicks and mammals. They are now classified in different subfamilies as they differ in the number of Ca2+ binding EF hands.

Oncomodulin is a parvalbumin-family calcium-binding protein expressed and secreted by macrophages.

Calmodulin-binding proteins are, as their name implies, proteins which bind calmodulin. Calmodulin can bind to a variety of proteins through a two-step binding mechanism, namely "conformational and mutually induced fit", where typically two domains of calmodulin wrap around an emerging helical calmodulin binding domain from the target protein.

<span class="mw-page-title-main">EF hand</span> Protein helix–loop–helix motif

The EF hand is a helix–loop–helix structural domain or motif found in a large family of calcium-binding proteins.

Ca<sup>2+</sup>/calmodulin-dependent protein kinase II

Ca2+
/calmodulin-dependent protein kinase II is a serine/threonine-specific protein kinase that is regulated by the Ca2+
/calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII is also necessary for Ca2+
 homeostasis and reuptake in cardiomyocytes, chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation.

Calexcitin is a calcium-binding protein first isolated from the sea snail Hermissenda crassicornis. It is upregulated following Pavlovian conditioning.

<span class="mw-page-title-main">Calretinin</span> Protein-coding gene in the species Homo sapiens

Calretinin, also known as calbindin 2, is a calcium-binding protein involved in calcium signaling. In humans, the calretinin protein is encoded by the CALB2 gene.

<span class="mw-page-title-main">Parvalbumin</span>

Parvalbumin (PV) is a calcium-binding protein with low molecular weight. In humans, it is encoded by the PVALB gene. It is not a member of the albumin family; it is named for its size and its ability to coagulate.

<span class="mw-page-title-main">Inositol-trisphosphate 3-kinase</span> Class of enzymes

Inositol (1,4,5) trisphosphate 3-kinase (EC 2.7.1.127), abbreviated here as ITP3K, is an enzyme that facilitates a phospho-group transfer from adenosine triphosphate to 1D-myo-inositol 1,4,5-trisphosphate. This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:1D-myo-inositol-1,4,5-trisphosphate 3-phosphotransferase. ITP3K catalyzes the transfer of the gamma-phosphate from ATP to the 3-position of inositol 1,4,5-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate. ITP3K is highly specific for the 1,4,5-isomer of IP3, and it exclusively phosphorylates the 3-OH position, producing Ins(1,3,4,5)P4, also known as inositol tetrakisphosphate or IP4.

<span class="mw-page-title-main">S100-A1</span> Protein-coding gene in the species Homo sapiens

Protein S100-A1, also known as S100 calcium-binding protein A1 is a protein which in humans is encoded by the S100A1 gene. S100A1 is highly expressed in cardiac and skeletal muscle, and localizes to Z-discs and sarcoplasmic reticulum. S100A1 has shown promise as an effective candidate for gene therapy to treat post-myocardially infarcted cardiac tissue.

<span class="mw-page-title-main">Calcium-binding protein 1</span> Protein-coding gene in the species Homo sapiens

Calcium binding protein 1 is a protein that in humans is encoded by the CABP1 gene. Calcium-binding protein 1 is a calcium-binding protein discovered in 1999. It has two EF hand motifs and is expressed in neuronal cells in such areas as hippocampus, habenular nucleus of the epithalamus, Purkinje cell layer of the cerebellum, and the amacrine cells and cone bipolar cells of the retina.

<span class="mw-page-title-main">STIM2</span> Protein-coding gene in the species Homo sapiens

Stromal interaction molecule 2 (STIM2) is a protein that in humans is encoded by the STIM2 gene.

<span class="mw-page-title-main">Regucalcin</span> Protein-coding gene in the species Homo sapiens

Regucalcin is a protein that in humans is encoded by the RGN gene

References

  1. ↑ Kinjo, Tashi G; Schnetkamp, Paul PM. Ca2+ Chemistry, Storage and Transport in Biologic Systems: An Overview. Madame Curie Bioscience Database [Internet]. Retrieved 2 May 2016.
  2. 1 2 Yáñez M, Gil-Longo J, Campos-Toimil M (2012). "Calcium binding proteins". Adv Exp Med Biol. Advances in Experimental Medicine and Biology. 740: 461–82. doi:10.1007/978-94-007-2888-2_19. ISBN   978-94-007-2887-5. PMID   22453954.
  3. ↑ Siegel, George (Ed.). Basic neurochemistry: molecular, cellular and medical aspects. Lippincott Williams and Wilkins / 1999 ISBN   0-397-51820-X
  4. ↑ "NordiQC". Archived from the original on 2016-06-20. Retrieved 2016-05-04.
  5. 1 2 Ikura, Mitsuhiko; Osawa, Masanori; Ames, James B. (July 2002). "The role of calcium-binding proteins in the control of transcription: structure to function" (PDF). BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology. 24 (7): 625–636. doi:10.1002/bies.10105. PMID   12111723 . Retrieved 5 November 2022.
  6. ↑ Kawasaki, Kazuhiko (2018). "The Origin and Early Evolution of SCPP Genes and Tissue Mineralization in Vertebrates". Biomineralization. pp. 157–164. doi: 10.1007/978-981-13-1002-7_17 . ISBN   978-981-13-1001-0. S2CID   91544812.
  7. ↑ Nelson T, Cavallaro S, Yi C, McPhie D, Schreurs B, Gusev P, Favit A, Zohar O, Kim J, Beushausen S, Ascoli G, Olds J, Neve R, Alkon D (1996). "Calexcitin: a signaling protein that binds calcium and GTP, inhibits potassium channels, and enhances membrane excitability". PNAS . 93 (24): 13808–13. Bibcode:1996PNAS...9313808N. doi: 10.1073/pnas.93.24.13808 . PMC   19433 . PMID   8943017.
  8. 1 2 Mojumder DK, Wensel TG, Frishman LJ (Aug 2008). "Subcellular compartmentalization of two calcium binding proteins, calretinin and calbindin-28 kDa, in ganglion and amacrine cells of the rat retina". Molecular Vision. 14: 1600–1613. PMC   2528027 . PMID   18769561.
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