CELA3A

What is CELA3A Protein?

CELA3A, known as chymotrypsin-like elastase 3A, is a serine proteinase in the elastase sub-family. It primarily expresses in the pancreas and is secreted as an inactive precursor. Unlike other elastases, CELA3A lacks significant elastolytic activity. Instead, it specializes in cleaving proteins at alanine residues, aiding digestion in the gut. Additionally, CELA3A might play a role in cholesterol transport and metabolism within the intestines. Alongside CELA3B, it’s sometimes referred to as protease E or elastase 1. This protein is crucial in human physiology, especially concerning gastrointestinal functions.

What is the Function of CELA3A Protein?

CELA3A, or chymotrypsin-like elastase 3A, is a serine protease belonging to the elastase subfamily. Among the six human elastase genes, CELA3A stands out due to its minimal ability to break down elastin. CELA3A has a similar structure to elastases 1, 2, 2A, 2B, and 3B. Normally, it’s released from the pancreas in its inactive form and helps with digestion in the intestines, acting like other serine proteases such as trypsin, chymotrypsin, and kallikrein. Its main activity is cutting proteins at alanine residues, and it might also play a part in cholesterol transport and metabolism in the gut. Thus, CELA3A is crucial for protein digestion and lipid metabolism in the digestive system.

CELA3A Related Signaling Pathway

CELA3A, also called chymotrypsin-like elastase 3A, is a serine protease known for its role in digestion. It mainly acts in the digestive system, specifically breaking down proteins in the intestines. CELA3A targets proteins, particularly at sites with alanine residues, showing a unique substrate preference during protein digestion. It’s also thought to have a part in cholesterol transport and fat metabolism within the intestines, hinting at its involvement in lipid metabolic pathways. While its direct connections to signaling pathways like Hippo or NF-κB are unclear, the role of CELA3A in digestion and metabolism may intersect with these pathways, especially regarding cell growth and metabolism regulation. Thus, the primary function of CELA3A is linked to digestive processes and lipid metabolism in the digestive system.

CELA3A Related Diseases

CELA3A, a serine protease with digestive functions, is linked to various diseases, particularly those affecting the digestive system and certain cancers. In the intestines, CELA3A primarily aids in digesting proteins by cleaving them at alanine residues. Additionally, it might play a role in transporting and metabolizing cholesterol in the gut, which could impact lipid metabolism disorders. In cancer, CELA3A expression varies among types like pancreatic, breast, cervical, and colorectal cancers. While not a prognostic marker, its expression patterns in specific cancers could relate to tumor progression. Thus, CELA3A is considered a crucial target for studying and treating digestive and cancer-related diseases.

Bioapplications of CELA3A

Recombinant CELA3A, a serine protease, finds varied applications in research, industrial production, and medicine. In scientific studies, it’s recognized for its role as an alanine-specific enzyme with limited elastolytic activity, used to explore protein digestion mechanisms and cholesterol metabolism. In industry, its recombinant forms are synthesized using systems like yeast, E. coli, and mammalian cells, often with a His-tag for easy purification and detection. Medically, CELA3A is linked to pancreatic and lipid metabolism disorders. Understanding its function can shed light on its role in these conditions, potentially guiding the development of new treatment approaches. Thus, recombinant CELA3A is vital in both advancing scientific insights and enhancing clinical applications.

Case Study 1: Párniczky A. et al. Int J Mol Sci. 2016

CELA3A and CELA3B, human chymotrypsin-like elastases, are nearly identical genes that result from duplication. CELA3B readily forms complexes with certain proenzymes, but CELA3A doesn’t due to a specific amino acid switch. Testing for variations at this site in chronic pancreatitis patients yielded no significant findings about risk. In a study of 225 patients and 300 controls, allele frequencies of certain variants showed no noteworthy difference. We found some genetic variants, but none linked to pancreatitis risk. Variations at amino-acid position 241 don’t seem to impact the development of chronic pancreatitis.

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  Fig1. Densitometric quantitation of secreted CELA3A and CELA3B.
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  Fig2. Activity of CELA3A and CELA3B variants in the conditioned medium of transfected HEK 293T cells.

Case Study 2: Szabó A. et al. J Biol Chem. 2016

In the pancreas, digestive proenzymes are usually released in their singular forms. However, in animals like cattle, there’s a unique complex involving various proenzymes. For humans and pigs, we know they have binary complexes of procarboxypeptidase A (proCPA) with proelastases. We tested various human pancreatic enzyme precursors to see how they interact. ProCELA3B had strong connections with proCPA1 and even tighter with proCPA2, in contrast to proCELA2A, which showed weak binding only to proCPA1. Interestingly, proCELA3A, although similar to proCELA3B, didn’t form stable complexes due to a minor amino acid difference. This genetic variation hints at individual differences in how these enzymes behave. The enzyme activity was largely unchanged, apart from delaying procarboxypeptidase activation. So, human pancreatic enzyme complex formation is limited mostly to certain proelastases and procarboxypeptidases, enhancing enzyme stability and activation control.

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  Fig3. Binding of proCELA2A and proCELA3A to proCPA1.
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  Fig4. Binding of proCELA3A mutant G241A to proCPA1 and proCPA2.

CELA3A has several biochemical functions, for example, serine-type endopeptidase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CELA3A itself. We selected most functions CELA3A had, and list some proteins which have the same functions with CELA3A. You can find most of the proteins on our site.

Function	Related Protein
serine-type endopeptidase activity	GZMH,KLK1B22,KLK1B8,F9B,MASP1,KLK1B9,CTSG,MMP8,C1R,PRSS38

CELA3A has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CELA3A here. Most of them are supplied by our site. Hope this information will be useful for your research of CELA3A.

CREB3