Protein O-mannosyl transferase 1

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Protein O-mannosyl transferase 1
Properties of human protein
Mass / length primary structure 461 AA
Cofactor Mg ++
Isoforms 4th
Identifier
Gene name POMT1
External IDs
Enzyme classification
EC, category 2.4.1.109 ,  glycosyl transferase
Response type Transfer of a mannosyl residue
Substrate Dolichyl phosphate D-mannose + protein
Products Dolichyl phosphate + O-mannosyl protein
Occurrence
Parent taxon Eukaryotes , bacteria

Protein-O-mannosyl transferase 1 (POMT1, English protein O-mannosyl transferase 1) is an enzyme in eukaryotes that belongs to the group of glycosyl transferases . It is through the POMT1 gene encoding that in humans on the long arm of chromosome 9 is located (9q34.13). Mutations in this gene can lead to rare hereditary diseases. POMT1 is involved in the so-called O-glycosylation of proteins .

The enzyme is anchored as a “multipass” transmembrane protein in the lipid bilayer of the endoplasmic reticulum and is formed ( expressed ) in numerous cells . A high concentration was found in the testes, heart muscle, and pancreas. Lower concentrations are found in the kidneys, skeletal muscle, brain, placenta, lungs, and liver.

function

POMT1 can only become enzymatically active if it is present as a protein complex with another glycosyltransferase, protein O-mannosyltransferase 2 (POMT2). POMT1 and POMT2 together catalyze the binding of the sugar mannose via an O-glycosidic bond to the serine / threonine side chains of the protein. This is an important step in the post-translational modification of proteins.

Medical importance

In mammals, O-mannosylglycans are found mainly in the α-dystroglycan . α-Dystroglycan is an important component of the dystrophin-glycoprotein complex in muscle and nerve cells, which is used to connect the cytoskeleton with the extracellular matrix. Mutations in the POMT1 gene or POMT2 gene disrupt the O-glycosylation of the α-dystroglycan, so that diseases can occur. Several diseases or phenotypes belonging to the group of dystroglycanopathies are known that are associated with mutations in the POMT1 gene :

further reading

Individual evidence

  1. ↑ UniProt search EC: 2.4.1.109 by taxonomy
  2. ↑ POMT1.  In: Online Mendelian Inheritance in Man . (English)
  3. ↑ a b UniProt Q9Y6A1
  4. ↑ a b B. Prados, A. Peña et al. a .: Expression of the murine Pomt1 gene in both the developing brain and adult muscle tissues and its relationship with clinical aspects of Walker-Warburg syndrome. In: The American Journal of Pathology , Volume 170, Number 5, May 2007, pp. 1659-1668, doi : 10.2353 / ajpath.2007.061264 . PMID 17456771 . PMC 185496 (free full text).
  5. ↑ D. Beltrán-Valero de Bernabé, S. Currier et al. a .: Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome. In: American Journal of Human Genetics Volume 71, Number 5, November 2002, pp. 1033-1043, doi : 10.1086 / 342975 . PMID 12369018 . PMC 419999 (free full text).
  6. ↑ DS Kim, YK Hayashi et al. a .: POMT1 mutation results in defective glycosylation and loss of laminin-binding activity in alpha-DG. In: Neurology Volume 62, Number 6, March 2004, pp. 1009-1011, PMID 15037715 .
  7. ↑ C. Godfrey, E. Clement et al. a .: Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. In: Brain: a journal of neurology Volume 130, Pt 10 October 2007, pp. 2725-2735, doi : 10.1093 / brain / awm212 . PMID 17878207 .
  8. ↑ E. Mercuri, S. Messina et al. a .: Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study. In: Neurology Volume 72, Number 21, May 2009, pp. 1802-1809, doi : 10.1212 / 01.wnl.0000346518.68110.60 . PMID 19299310 .
  9. ↑ MDDGA1.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ MDDGB1.  In: Online Mendelian Inheritance in Man . (English)
  11. ↑ LGMD2K.  In: Online Mendelian Inheritance in Man . (English)