Histone Serine/threonine/tyrosine phosphatases

Proteins that catalyse the removal of phosphate groups from the target proteins are called phosphatases. They are functionally of 2 types: one that dephosphorylate serine/threonine residues; others that dephosphorylate tyrosine residues.

Serine/Threonine phosphatases are metalloenzymes (presence of Mn/Fe/Zn in the catalytic site) and can be classified under two families:

PPP family that include members like PP1, PP2A and PP2B and...

PPM family that includes PP2C.

Mechanism of catalysis is almost the same in both families. Water molecules activated by metal ions attack the phosphorus of phosphate group and undergo an SN2 mechanism to dephosphorylate the targets residue with the help of neighbouring histidine residue.

On the other hand, Tyrosine phosphatases can be divided into 4 main families:

Tyrosine-specific phosphatase family,

VH1-like dual-specificity phosphatase family,

cdc25 family, and

Low molecular weight phosphatase family.

Tyrosine phosphatases harbour a cysteine containing motif (CX5R) that accepts phosphate group from the substrate. Phosphate group is later hydrolysed to free the enzyme. An important entry is the DUSP1 that has been reported to dephosphorylate both Ser/Thr and Tyr residues.

Histone dephosphorylases play a significant role in DNA damage repair pathways by dephosphorylating histone gamma-H2AX (phosphorylated form of H2AX) after successful DNA damage response has been elicited. This becomes part of cellular homeostasis. They are also supposedly involved in microtubule organisation.

Further reading: PMID: 8987393, PMID: 8987394.

Cytogenetic map of Serine/threonine/tyrosine phosphatases coding genes
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Different histone Serine/threonine/tyrosine phosphatases
Enzyme (UniprotKB recommended name) Coding gene/s Site of histone modification
Dual specificity protein phosphatase 1DUSP1H3S10ph
Eyes absent homolog 1EYA1H2AY142ph
Eyes absent homolog 2EYA2H2AY142ph
Eyes absent homolog 3EYA3H2AY142ph
Protein phosphatase 1DPPM1DH2AS139ph
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformPPP2CAH2AS139ph
Serine/threonine-protein phosphatase 2A catalytic subunit beta isoformPPP2CBH2AS139ph
Serine/threonine-protein phosphatase 4 catalytic subunitPPP4CH2AS139ph
Serine/threonine-protein phosphatase 5PPP5C
Serine/threonine-protein phosphatase PP1-gamma catalytic subunitPPP1CCH3T11ph