Phosphomannomutase 1,2 (PMM1,2)

Reference work entry


Phosphomannomutase (PMM) belongs to the family of isomerases and is involved in early mannose metabolism. It is ubiquitous and found in microbes, plants, and animals. It reversibly catalyzes the conversion of mannose-6-phosphate (Man-6-P) to mannose-1-phosphate (Man-1-P) that is required for GDP-mannose (GDP-Man) and dolichol phosphate mannose (Dol-P-Man) synthesis. GDP-mannose is essential for N-glycosylation of proteins, microbial cell wall polysaccharides, and L-ascorbic acid synthesis in plants. Dol-P-Man is required for N-glycosylation, GPI anchors O- and C-mannosylation. In many organisms, a single gene encodes both PMM and phosphoglucomutase (PGM) activities. PGM interconverts 1- and 6-glucose phosphate isomers. The presence of such bifunctional PMM/PGM enzymes in T. brucei, G. lamblia, P. aeruginosa, etc., is an example of evolutionary convergence (Lee et al. 2012). There are two mammalian isozymes – PMM1 and PMM2. We will focus mainly on human PMM2 due to its medical relevance and compare it with PMM1 in certain instances.


Nicotinamide Adenine Dinucleotide Phosphate Nicotinamide Adenine Dinucleotide Phosphate Phosphomannose Isomerase Inositol Monophosphate Mannose Phosphate Isomerase 


  1. Cline A, Gao N, Flanagan-Steet H, Sharma V, Rosa S, Sonon R, Azadi P, Sadler KC, Freeze HH, Lehrman MA, Steet RA (2012) Zebrafish model of PMM2-CDG reveals altered neurogenesis and a substrate-accumulation mechanism for N-Linked glycosylation deficiency. Mol Biol Cell 23(21):4175–4187. doi:10.1091/mbc.E12-05-0411, PMID: 22956764PubMedCentralPubMedCrossRefGoogle Scholar
  2. Cromphout K, Vleugels W, Heykants L, Schollen E, Keldermans L, Sciot R, D’Hooge R, De Deyn PP, von Figura K, Hartmann D, Körner C, Matthijs G (2006) The normal phenotype of Pmm1-deficient mice suggests that Pmm1 is not essential for normal mouse development. Mol Cell Biol 26:5621–5635. doi:10.1128/MCB.02357-05, PMID: 16847318PubMedCentralPubMedCrossRefGoogle Scholar
  3. Freeze HH, Eklund EA, Ng BG, Patterson MC (2012) Neurology of inherited glycosylation disorders. Lancet Neurol 11:453–466, PMID: 22516080PubMedCentralPubMedCrossRefGoogle Scholar
  4. Glaser L, Kornfeld S, Brown DH (1959) Preparation and properties of phospho-mannomutase from Baker’s yeast. Biochemica et Biophysica Acta 33:522–526. doi:10.1016/0006-3002(59)90143-X, PMID: 13670924CrossRefGoogle Scholar
  5. Gracy RW, Noltmann EA (1968) Studies on PhosphomannoseIsomerase: I. Isolation homogeneity, measurements and determination of some physical properties. J Biol Chem 243:3161–3168, PMID: 5653195PubMedGoogle Scholar
  6. Haeuptle MA, Hennet T (2009) Congenital Disorders of Glycosylation: an update on defects affecting the biosynthesis of dolichol linked oligosaccharides. Human Mutation 30:1628–1641. doi:10.1002/humu.21126, PMID 19862844Google Scholar
  7. Hansen SH, Frank SR, Casanova JE (1997) Cloning and characterization of human phosphomannomutase, a mammalian homologue of yeast SEC53. Glycobiology 7:829–834, PMID: 9376685PubMedCrossRefGoogle Scholar
  8. Heykants L, Schollen E, Grunewald S, Matthijs G (2001) Identification and localization of two mouse phosphomannomutase genes, Pmm1 and Pmm2. Gene 270:53–59, PMID 11404002Google Scholar
  9. Kepes F, Schekman R (1988) The yeast SEC53 gene encodes phosphomannomutase. J Biol Chem 283:9155–9161, PMID: 3288631Google Scholar
  10. Lee Y, Mick J, Furdui C, Beamer LJ (2012) A coevolutionary residue network at the site of a functionally important conformational change in a phosphohexomutase enzyme family. PLoS One 7(6):e38114. doi:10.1371/journal.pone. 0038114, PMID: 22685552PubMedCentralPubMedCrossRefGoogle Scholar
  11. Matthijs G, Schollen E, Pirard M, Budarf ML, Van Schaftingen E (1997a) PMM (PMM1), the human homologue of SEC53 or yeast phosphomannomutase, is localized on chromosome 22q13. Genomics 40(1):41–47. doi:10.1006/geno.1996.4536, Feb 15, PMID: 9070917PubMedCrossRefGoogle Scholar
  12. Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, Van Schaftingen E (1997b) Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate – deficient glycoprotein type 1 syndrome (Jaeken syndrome). Nat Gen 16:88–92, PMID: 9140401CrossRefGoogle Scholar
  13. Menniti M, Iuliano R, Amato R, Boito R, Corea M, Le Pera I, Gulletta E, Fuiano G, Perrotti N (2005) Serum and glucocorticoid-regulated kinase Sgk1 inhibits insulin-dependent activation of phosphomannomutase 2 in transfected COS-7 cells. Am J Physiol Cell Physiol 288:C148–C155. doi:10.1152/ajpcell.00284. 2004, PMID: 15342340PubMedGoogle Scholar
  14. Pirard M, Achouri Y, Collet JF, Schollen E, Matthijs G, Van Schaftingen E (1999) Kinetic properties and tissular distribution of mammalian phosphomannomutase isozymes. Biochem J 339:201–207, PMID: 10085245PubMedCrossRefGoogle Scholar
  15. Pirard M, Collet JF, Matthijs G, Van Schaftingen E (1997) Comparison of PMM1 with the phosphomannomutases expressed in rat liver and in human cells. FEBS Lett 411:251–254, PMID: 9271215PubMedCrossRefGoogle Scholar
  16. Schneider A, Thiel C, Rindermann J, DeRossi C, Popovici D, Hoffmann GF, Gröne HJ, Körner C (2011) Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in mice. Nat Med 18:71–73. doi:10.1038/nm.2548, PMID: 22157680PubMedCrossRefGoogle Scholar
  17. Schollen E, Pardon E, Heykants L, Renard J, Doggett NA, Callen DF, Cassiman JJ, Matthijs G (1998) Comparative analysis of the phosphomannomutase genes PMM1, PMM2 and PMM2Ψ: the sequence variation in the processed pseudo-gene is a reflection of the mutations found in the functional gene. Hum Mol Gen 7:157–164, PMID: 9425221PubMedCrossRefGoogle Scholar
  18. Sharma V, Freeze HH (2011) Mannose efflux from the cells: a potential source of mannose in blood. J Biol Chem 286:10193–10200. doi:10.1074/jbc.M110.194241, PMID: 21273394PubMedCrossRefGoogle Scholar
  19. Sharma V, Ichikawa M, He P, Scott DA, Bravo Y, Dahl R, Ng BG, Cosford ND, Freeze HH (2011) Phosphomannose isomerase inhibitors improve N-glycosylation in selected phosphomannomutase deficient fibroblasts. J Biol Chem 286:39431–39438. doi:10.1074/jbc.M110.194241, PMID: 21949237PubMedCrossRefGoogle Scholar
  20. Silvaggi NR, Zhang C, Lu Z, Dai J, Dunaway-Mariano D, Allen KN (2006) The X-ray crystal structures of human phosphomannomutase 1 reveal the structural basis of Congenital Disorder of Glycosylation Type 1a. J Biol Chem 281:14918–14926. doi:10.1074/jbc.M601505200, PMID: 16540464PubMedCrossRefGoogle Scholar
  21. Grunewald S (2009) The clinical spectrum of phosphomannomutase 2 deficiency (CDG-Ia). BBA 1792:827–834. doi:10.1016/j.bbadis.2009.01.003, PMID: 19272306PubMedGoogle Scholar
  22. Thiel C, Lübke T, Matthijs G, von Figura K, Körner C (2006) Targeted disruption of the mouse phosphomannomutase 2 gene causes early embryonic lethality. Mol Cell Biol 26:5615–5620. doi:10.1128/MCB.02391-05, PMID: 16847317PubMedCentralPubMedCrossRefGoogle Scholar
  23. Veiga-da-Cunha M, Vleugels W, Maliekal P, Matthijs G, Van Schaftingen E (2008) Mammalian Phosphomannomutase PMM1 Is the Brain IMP-sensitive Glucose-1,6-bisphosphatase. J Biol Chem 49:33988–33993. doi:10.1074/jbc. M805224200, PMID: 18927083CrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Sanford-Burnham Medical Research InstituteLa JollaUSA

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