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[Biochemistry](https://durgical.com/en/biochemistry/) · Topic

# Glycoproteins and protein glycosylation (N- and O-linked)

Many proteins get sugar chains attached in the ER and Golgi. The sugars help folding, sorting, stability, cell recognition and blood groups.

Updated 2026-11-01

## Key facts

- N-linked: the sugar chain is attached to the amide N of asparagine in the sequence Asn-X-Ser/Thr (X ≠ proline), in the rough ER, during translation.
- N-glycans start as a 14-sugar block (Glc₃Man₉GlcNAc₂) built on dolichol phosphate and moved whole to the protein by oligosaccharyltransferase (OST); it is then trimmed in the ER and Golgi.
- O-linked: sugars are added one by one to the OH of serine or threonine (or hydroxylysine in collagen) in the Golgi; mucins and proteoglycans are O-glycosylated.
- Functions: folding quality control (calnexin/calreticulin), lysosomal targeting (mannose 6-phosphate), half-life in plasma, receptors and cell adhesion (selectins), ABO blood groups.
- Tunicamycin blocks the first step of the dolichol pathway; defects in the pathway cause congenital disorders of glycosylation (CDG).

## In detail

- 1. On the cytosolic face of the ER, sugars are added to dolichol phosphate from nucleotide sugars (UDP-GlcNAc, GDP-mannose); the lipid then flips into the ER lumen and receives more mannose and glucose.
- 2. OST transfers the whole oligosaccharide to asparagine of the growing chain as it enters the ER.
- 3. Glucosidases I and II remove glucose; calnexin and calreticulin hold proteins with one glucose until they fold correctly (folding checkpoint). Misfolded proteins are sent to ER-associated degradation.
- 4. In the Golgi, mannose trimming and addition of GlcNAc, galactose, fucose and sialic acid create 'complex' glycans; some keep 'high-mannose' glycans.
- 5. Lysosomal enzymes receive mannose 6-phosphate in the cis-Golgi, the signal that sends them to lysosomes.
- 6. Glycation is different: a non-enzymatic attachment of glucose to proteins (for example HbA1c and advanced glycation end-products in diabetes).

## Memory aid

N for asparagiNe (in the ER, en bloc); O for serine/thrEOnine OH (in the Golgi, one by one).

**Also called**
N-glycosylation, O-glycosylation, Dolichol pathway, Glycoproteins

## Clinical notes

- Congenital disorders of glycosylation (for example PMM2-CDG) cause multisystem disease; transferrin isoelectric focusing is the screening test.
- I-cell disease is a defect of mannose 6-phosphate tagging: lysosomal enzymes are secreted into blood instead of reaching lysosomes.
- Sialylated mucins and altered glycans are tumour markers (CA-125, CA 19-9 recognise carbohydrate-rich epitopes).

## Related conditions

- [Congenital disorder of glycosylation type Ia (PMM2-CDG)](https://durgical.com/en/conditions/congenital-disorder-of-glycosylation-type-ia/)
- [I-cell disease (mucolipidosis II)](https://durgical.com/en/conditions/i-cell-disease/)
- [Hurler syndrome (mucopolysaccharidosis type I)](https://durgical.com/en/conditions/hurler-syndrome/)

## Related

- [Protein targeting and signal sequences](https://durgical.com/en/biochemistry/topics/protein-targeting-and-signal-sequences/)
- [Molecular chaperones and heat shock proteins](https://durgical.com/en/biochemistry/topics/molecular-chaperones-and-heat-shock-proteins/)
- [Mannose 6-phosphate tagging (sending enzymes to the lysosome)](https://durgical.com/en/biochemistry/topics/mannose-6-phosphate-tagging/)
- [Glycosaminoglycans (mucopolysaccharides)](https://durgical.com/en/biochemistry/topics/glycosaminoglycans/)
- [Cell organelles and their metabolism](https://durgical.com/en/biochemistry/topics/cell-organelles-and-their-metabolism/)
- [Collagen synthesis](https://durgical.com/en/biochemistry/topics/collagen-synthesis/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)
- [Carbohydrate chemistry](https://durgical.com/en/biochemistry/topics/carbohydrate-chemistry/)
- [Translation and the genetic code](https://durgical.com/en/biochemistry/topics/translation-and-the-genetic-code/)

## Test yourself

Think of the answer, then tap the question to see it.

## To which amino acid is an N-linked glycan attached, and in which sequence?

To asparagine, in the sequon Asn-X-Ser/Thr where X is any amino acid except proline.

## What lipid carries the oligosaccharide before it is transferred to the protein?

Dolichol phosphate (dolichol pyrophosphate–oligosaccharide), in the ER membrane.

## Where and how does O-glycosylation take place?

Mainly in the Golgi, adding sugars one at a time to the hydroxyl of serine or threonine.

## What role do calnexin and calreticulin play?

They are lectin chaperones that hold monoglucosylated glycoproteins in the ER until they fold correctly.

## Which test screens for congenital disorders of glycosylation?

Isoelectric focusing of serum transferrin, which shows the loss of sialic acid-containing glycans.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [PDB-101: Molecule of the Month: Oligosaccharyltransferase](https://pdb101.rcsb.org/motm/266) (RCSB Protein Data Bank (PDB-101), 2026); [STT3A: Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3A (human)](https://www.uniprot.org/uniprotkb/P46977/entry) (UniProt, 2026); [PMM2-congenital disorder of glycosylation: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/pmm2-congenital-disorder-of-glycosylation/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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