Phosphatase Family HP1

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Phosphatase Classification: Fold HP: Superfamily HP: HP, branch1 family

HP1 is one of two major families within the Histidine Phosphatase fold, that uses a pHis intermediate during catalysis. HP1 includes several non-protein phosphatases, and two protein phosphatase subfamilies: PGAM5 is a serine phosphatase and STS (TULA or UBASH3) is a tyrosine phosphatase.

Subfamilies found in human


PGAMs mainly function as glycolytic enzymes regulating intracellular levels of their substrate 3-phosphoglycerate and product 2-phosphoglycerate. Human BPGM is a 2,3-bisphosphoglycerate mutase. They are found throughout most eukaryotes.

PGAM5: serine phosphatase at inner mitochondria membrane

PGAM5 is a protein serine phosphatase conserved in metazoa. It localized to inner mitochondria membrane. It has distinct substrates, such as ASK1, Drp1, FUNDC1. PGAM5 is involved in mitophagy regulation.

TIGAR: TP53 Induced Glycolysis and Apoptosis Regulatory phosphatase

TIGAR inhibits glycolysis and negatively modulates the level of intracellular reactive oxygen species (ROS), therefore regulating autophagy and apoptosis. TIGAR is found in chordates some basal eumetazoa, but is absent from nematodes and arthropods.

STS (TULA or UBASH3): tyrosine phosphatase

STS is a protein tyrosine phosphatase involved in T-cell receptor signaling. In particular, STS dephosphorylates the Syk subfamily kinases Syk and ZAP-70. STS is conserved in metazoa, but C. elegans lost the signature domains, SH3 and H2 domain, which are common among STSs.


PFKFB is a bifunctional enzyme responsible for the synthesis (as kinase) and degradation (as phosphatase) of fructose-2,6-bisphosphate a glycolytic regulator.

Other subfamilies


TFC7 is a RNA pol III transcription initiation factor complex (TFIIIC) subunit found in fungi and Dictyostelium.


HP1LE subfamily is found in choanoflagellates and sponge, but is absent from eumetazoa. Its function is unclear.