PROSITE documentation PDOC00158
Phosphoglycerate mutase family phosphohistidine signature


Phosphoglycerate mutase (EC (PGAM) and bisphosphoglycerate mutase (EC (BPGM) are structurally related enzymes which catalyze reactions involving the transfer of phospho groups between the three carbon atoms of phosphoglycerate [1,2]. Both enzymes can catalyze three different reactions, although in different proportions:

  • The isomerization of 2-phosphoglycerate (2-PGA) to 3-phosphoglycerate (3- PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer of the reaction.
  • The synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer.
  • The degradation of 2,3-DPG to 3-PGA (phosphatase EC activity).

In mammals, PGAM is a dimeric protein. There are two isoforms of PGAM: the M (muscle) and B (brain) forms. In yeast, PGAM is a tetrameric protein. BPGM is a dimeric protein and is found mainly in erythrocytes where it plays a major role in regulating hemoglobin oxygen affinity as a consequence of controlling 2,3-DPG concentration.

The catalytic mechanism of both PGAM and BPGM involves the formation of a phosphohistidine intermediate [3].

The bifunctional enzyme 6-phosphofructo-2-kinase / fructose-2,6-bisphosphatase (EC and EC (PF2K) [4] catalyzes both the synthesis and the degradation of fructose-2,6-bisphosphate. PF2K is an important enzyme in the regulation of hepatic carbohydrate metabolism. Like PGAM/BPGM, the fructose-2,6-bisphosphatase reaction involves a phosphohistidine intermediate and the phosphatase domain of PF2K is structurally related to PGAM/BPGM.

The bacterial enzyme α-ribazole-5'-phosphate phosphatase (gene cobC) which is involved in cobalamin biosynthesis also belongs to this family [5].

We built a signature pattern around the phosphohistidine residue.


Some organisms harbor a form of PGAM independent of 2,3-DPG, this enzyme is not related to the family described above [6].

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

PG_MUTASE, PS00175; Phosphoglycerate mutase family phosphohistidine signature  (PATTERN)


1AuthorsLe Boulch P. Joulin V. Garel M.-C. Rosa J. Cohen-Solal M.
SourceBiochem. Biophys. Res. Commun. 156:874-881(1988).

2AuthorsWhite M.F. Fothergill-Gilmore L.A.
TitleSequence of the gene encoding phosphoglycerate mutase from Saccharomyces cerevisiae.
SourceFEBS Lett. 229:383-387(1988).
PubMed ID2831102

3AuthorsRose Z.B.
SourceMethods Enzymol. 87:43-51(1982).

4AuthorsBazan J.F. Fletterick R.J. Pilkis S.J.
TitleEvolution of a bifunctional enzyme: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
SourceProc. Natl. Acad. Sci. U.S.A. 86:9642-9646(1989).
PubMed ID2557623

5AuthorsO'Toole G.A. Trzebiatowski J.R. Escalante-Semerena J.C.
SourceJ. Biol. Chem. 269:26503-26511(1994).

6AuthorsGrana X. de Lecea L. el-Maghrabi M.R. Urena J.M. Caellas C. Carreras J. Puigdomenech P. Pilkis S.J. Climent F.
TitleCloning and sequencing of a cDNA encoding 2,3-bisphosphoglycerate-independent phosphoglycerate mutase from maize. Possible relationship to the alkaline phosphatase family.
SourceJ. Biol. Chem. 267:12797-12803(1992).
PubMed ID1535626

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