What is the Difference Between Proteoglycans and Glycosaminoglycans

The main difference between proteoglycans and glycosaminoglycans is that proteoglycans are heavily glycosylated proteins, consisting of a “core protein” with one or more covalently attached glycosaminoglycan (GAG) chains, whereas glycosaminoglycans are long linear polysaccharides with repeating disaccharide units.   

Proteoglycans and glycosaminoglycans are two components of the extracellular matrix and cell surfaces. Their main function is to provide tensile strength and hydration to resist compressive forces.

Key Areas Covered

  1. What are Proteoglycans
    • Definition, Structure, Function
  2. What are Glycosaminoglycans
    • Definition, Structure, Function
  3. Similarities Between Proteoglycans and Glycosaminoglycans
    • Outline of Common Features
  4. Difference Between Proteoglycans and Glycosaminoglycans
    • Comparison with Key Differences

Key Terms

Glycosaminoglycans, ProteoglycansProteoglycans vs Glycosaminoglycans - Comparison Summary

What are Proteoglycans

Proteoglycans are glycoconjugates, biomolecules with a core protein covalently attached to glycosaminoglycan (GAG) chains. The point of attachment of GAGs to proteoglycans is a serine residue (Ser). The GAG joins the proteoglycan through a tetrasaccharide bridge (e.g. chondroitin sulfate-GlcA-Gal-Gal-Xyl-PROTEIN). The Ser residue is generally in the sequence -Ser-Gly-X-Gly- (where X can be any amino acid residue but proline), although not every protein with this sequence has an attached glycosaminoglycan. The GAG chains are long, linear, negatively charged, and heavily hydrated carbohydrate polymers under physiological conditions due to the occurrence of sulfate and uronic acid groups.

Compare Proteoglycans and Glycosaminoglycans - What's the difference?

Figure 1: Proteoglycans

Furthermore, proteoglycans occur in connective tissue. They are the main component of the extracellular matrix of animals. In addition, proteoglycans form large complexes such as hyaluronan and collagen-like fibrous matrix complexes. Collagen and other proteoglycans in combination form cartilage. On the other hand, the negative charges of proteoglycans can bind with cations to regulate the movement of molecules through the extracellular matrix. This allows the stabilization of signaling molecules and proteins inside the extracellular matrix. Further, the hydrated gel of the proteoglycans serves as a lubricant, withstanding high pressure. In bacteria, proteoglycans allow cell adhesion and colonization.

What are Glycosaminoglycans

Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units. Uronic sugar and amino sugar are the two sugar units in the repeating disaccharide units. However, in the sulfated glycosaminoglycan, keratan contains a galactose unit replacing the uronic sugar. One of the main features of glycosaminoglycans is that they can serve as lubricants and shock absorbers due to their highly polar nature of the glycosaminoglycans. More importantly, glycosaminoglycans occur in vertebrates, invertebrates, and bacteria.

Proteoglycans vs Glycosaminoglycans

Figure 2: Repeating Unit in Glycosaminoglycans

Moreover, the formation of glycosaminoglycans is an enzymatic action and due to that, they vary greatly in size, disaccharide structure, and sulfation. According to their disaccharide structure, there are four types of glycosaminoglycans: heparin, chondroitin sulfate, keratan sulfate, and hyaluronic acid. However, along with the protein interactions with heparin-binding proteins, chondroitin sulfate allows cell proliferation in wound repair. In contrast, keratan sulfate maintains tissue hydration. Further, hyaluronic acid is a major component of synovial tissue and fluid and it binds cells together, lubricates joints, and helps maintain the shape of the eyeballs.   

Similarities Between Proteoglycans and Glycosaminoglycans

  • Proteoglycans and glycosaminoglycans are two structural components of the extracellular matrix of animals and bacteria.
  • They contain repeating units and are formed by an enzymatic reaction.
  • The main function of proteoglycans and glycosaminoglycans is hydration and lubrication.

Difference Between Proteoglycans and Glycosaminoglycans


Proteoglycans refer to compounds consisting of a protein bonded to mucopolysaccharide groups, present especially in connective tissue, while glycosaminoglycans are any of a group of compounds occurring chiefly as components of connective tissue and are complex polysaccharides containing amino groups.


Usually, proteoglycans are heavily glycosylated proteins while glycosaminoglycans are long, linear polysaccharides consisting of repeating disaccharide units.


Proteoglycans are glycosylated proteins while glycosaminoglycans are responsible for the glycosylation of proteoglycans.


Proteoglycans regulate the movement of molecules in the extracellular matrix while glycosaminoglycans hydrate and lubricate the extracellular matrix.


In brief, proteoglycans and glycosaminoglycans are two substances that occur in the extracellular matrix in animals. They also occur in bacteria. Proteoglycans are heavily glycosylated proteins. The glycosylation of proteoglycans is by glycosaminoglycans or mucopolysaccharides. Additionally, the main function of proteoglycans is to allow the movement of molecules across the extracellular matrix. In contrast, glycosaminoglycans are long, linear polysaccharides, with repeating disaccharide units. Furthermore, the main function of glycosaminoglycans is to lubricate and hydrate the extracellular matrix, allowing it to withstand high pressure. Therefore, the main difference between proteoglycans and glycosaminoglycans is their structure and function.

  1. Varki A, Cummings R, Esko J, et al., editors. Essentials of Glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1999. Chapter 11, Proteoglycans and Glycosaminoglycans.
Image Courtesy:
  1. Extracellular Matrix Components of Cartilage” By Kassidy Veasaw – Own work (CC BY-SA 4.0) via Commons Wikimedia
  2. Chondroitin Sulfate Structure NTP” By Prithason at English Wikipedia – Own Work (Public Domain) 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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