{PDOC00158}
{PS00175; PG_MUTASE}
{BEGIN}
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* Phosphoglycerate mutase family phosphohistidine signature *
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Phosphoglycerate  mutase (EC 5.4.2.1) (PGAM)  and  bisphosphoglycerate  mutase
(EC 5.4.2.4) (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 3.1.3.13 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 2.7.1.105 and EC 3.1.3.46) (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 alpha-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.

-Consensus pattern: [LIVM]-x-R-H-G-[EQ]-x-{Y}-x-N
                    [H is the phosphohistidine residue]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for Haemophilus influenzae PGAM.
-Other sequence(s) detected in Swiss-Prot: 2.

-Note: 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.

[ 1] Le Boulch P., Joulin V., Garel M.-C., Rosa J., Cohen-Solal M.
     Biochem. Biophys. Res. Commun. 156:874-881(1988).
[ 2] White M.F., Fothergill-Gilmore L.A.
     "Sequence of the gene encoding phosphoglycerate mutase from
     Saccharomyces cerevisiae."
     FEBS Lett. 229:383-387(1988).
     PubMed=2831102
[ 3] Rose Z.B.
     Methods Enzymol. 87:43-51(1982).
[ 4] Bazan J.F., Fletterick R.J., Pilkis S.J.
     "Evolution of a bifunctional enzyme:
     6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
     Proc. Natl. Acad. Sci. U.S.A. 86:9642-9646(1989).
     PubMed=2557623
[ 5] O'Toole G.A., Trzebiatowski J.R., Escalante-Semerena J.C.
     J. Biol. Chem. 269:26503-26511(1994).
[ 6] Grana X., de Lecea L., el-Maghrabi M.R., Urena J.M., Caellas C.,
     Carreras J., Puigdomenech P., Pilkis S.J., Climent F.
     "Cloning and sequencing of a cDNA encoding
     2,3-bisphosphoglycerate-independent phosphoglycerate mutase from
     maize. Possible relationship to the alkaline phosphatase family."
     J. Biol. Chem. 267:12797-12803(1992).
     PubMed=1535626

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