What is the Difference Between Thrombin and Prothrombin

The main difference between thrombin and prothrombin is that thrombin is the product of proteolytic activation of prothrombin, whereas prothrombin is the precursor of thrombin.  

Thrombin and prothrombin are two substances responsible for blood clotting, a process important for preventing bleeding when injured.

Key Areas Covered

1. What is Thrombin
– Definition, Facts, Function
2. What is Prothrombin
– Definition, Facts, Function
3. Similarities Between Thrombin and Prothrombin
– Outline of Common Features
4. Difference Between Thrombin and Prothrombin
– Comparison of Key Differences

Key Terms  

Prothrombin, Thrombin

Difference Between Thrombin and Prothrombin - Comparison Summary

What is Thrombin

Thrombin is a serine protease that has an opposing role in blood clotting. Na+ ions are the major activator of the thrombin, but the cleavage of anticoagulant protein C is important for the function of the enzyme. Additionally, the enzyme is allosterically controlled by the cofactor thrombomodulin. Blood coagulation is a specialization of the complement system. Also, it is an immune response with developmental enzyme cascades. The activated form of thrombin contains a chymotrypsin-like protein fold formed by the asymmetric association of two six-stranded β-barrels. However, the catalytic triad of thrombin contains H57, D102 and S195. Out of which, two residues come from the N-terminal β-barrel, and the other is from the C-terminal β-barrel.

Compare Thrombin and Prothrombin

Figure 1: Coagulation

Furthermore, thrombin is one of the most intensively studied proteases. Thrombin is synthesized in the liver and secreted into the general circulation as prothrombin or (zymogen). The activation of thrombin occurs at the site of vascular injury. It starts the coagulation cascade.   

What is Prothrombin

Prothrombin is the central protein involved in blood clotting, a greatly important physiological reaction. It serves as the precursor to thrombin. Also, it activates with the binding of Na+ to the protein. However, naturally occurring mutations in the prothrombin gene affect the binding of Na+.

Thrombin vs Prothrombin

Figure 2: Mutant Human Prothrombin

Moreover, the prothrombin test is important in evaluating the coagulation state of patients. It evaluates the extrinsic and common pathways of coagulation. It detects the deficiency of factors II, V, VII, and X. Also, it detects the low fibrinogen concentration. It measures the time taken for plasma to clot after the addition of thromboplastin. Prolonged prothrombin time can diagnose liver disease, vitamin K deficiency, factor deficiency, etc.

Similarities Between Thrombin and Prothrombin

  • Thrombin and prothrombin are two substances important for blood clotting.
  • They prevent excess bleeding in injuries.
  • Both are proteins.

Difference Between Thrombin and Prothrombin


Thrombin is an enzyme in blood plasma that causes blood clotting by converting fibrinogen to fibrin. In contrast, prothrombin refers to a protein present in blood plasma that is converted into active thrombin during coagulation.


Thrombin contains two polypeptide chains of 36 (A chain) and 259 (B chain) residues that are covalently linked through a disulfide bond between residues C1 and C122, while prothrombin is a modular assembly that includes the N-terminal Gla domain (residues 1–46), kringle-1 (residues 65–143), kringle-2 (residues 170–248) and a C-terminal protease domain (residues 285–579).


Thrombin is produced by activating prothrombin, while prothrombin is synthesized in the liver.

Molecular Weight

The molecular weight of thrombin is 37 kDa, while the molecular weight of prothrombin is 72 kDa.


Thrombin is less complex, while prothrombin is more complex.


Thrombin is the active enzyme, while prothrombin is inactive.

Enzymatic Function

Thrombin converts fibrinogen into fibrin, while prothrombin has no enzymatic activity.


Thrombin undergoes allosteric regulation, while prothrombin does not undergo regulation.


In brief, thrombin and prothrombin are two proteins important for blood clotting. Thrombin is the enzyme that converts fibrinogen into fibrin. Also, it contains two polypeptide chains. In comparison, prothrombin is the precursor for thrombin. Additionally, it is a molecular assembly including the N-terminal Gla domain, kringle-1, kringle-2, and a C-terminal protease domain. Therefore, the main difference between thrombin and prothrombin is their structure and function.

  1. Di Cera E. Thrombin. Mol Aspects Med. 2008 Aug;29(4):203-54. doi: 10.1016/j.mam.2008.01.001. Epub 2008 Feb 1. PMID: 18329094; PMCID: PMC2491495.
  2. Yang R, Moosavi L. Prothrombin Time. [Updated 2022 Oct 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.
Image Courtesy:
  1. Fibrinogen to fibrin coagulation” By 5-HT2AR – Own Work (CC0) via Commons Wikimedia
  2. Human prothrombin mutant 5EDM open structure” By 5-HT2AR – Own work (CC0) via Commons Wikimedia

About the Author: Lakna

Lakna, a graduate in Molecular Biology and Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things. She has a keen interest in writing articles regarding science.

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