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| Enzyme (UniprotKB recommended name) | Coding gene/s | Site of histone modification |
|---|---|---|
| Dual specificity protein phosphatase 1 | DUSP1 | H3S10ph |
| Eyes absent homolog 1 | EYA1 | H2AY142ph |
| Eyes absent homolog 2 | EYA2 | H2AY142ph |
| Eyes absent homolog 3 | EYA3 | H2AY142ph |
| Protein phosphatase 1D | PPM1D | H2AS139ph |
| Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform | PPP2CA | H2AS139ph |
| Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform | PPP2CB | H2AS139ph |
| Serine/threonine-protein phosphatase 4 catalytic subunit | PPP4C | H2AS139ph |
| Serine/threonine-protein phosphatase 5 | PPP5C | |
| Serine/threonine-protein phosphatase PP1-gamma catalytic subunit | PPP1CC | H3T11ph |