Phosphatase classification

Phosphatases are classified by protein structural fold of the catalytic domain, and sub-classified by families and subfamilies based on the sequence of the phosphatase domains as well as by sequences outside of the catalytic domain, and known biochemical and biological functions [1].

Classification Chart of Protein Phosphatases

Fold	Superfamily	Family	Substrate	Present in human
CC1	CC1	PTP	pTyr	Yes
		DSP	pTyr, pSer/pThr, small molecule	Yes
		PTEN	lipid	Yes
		Myotubularin	lipid	Yes
		SAC	lipid	Yes
		Paladin	inactive	Yes
		OCA	?	No
CC2	CC2	LMWPTP	pTyr	Yes
		SSU72	pSer	Yes
		ArsC	Arsenate	No
CC3	CC3	CDC25	pTyr, pThr	Yes
HAD	HAD	EYA	pTyr	Yes
		FCP	pSer	Yes
		NagD	pTyr, pSer	Yes
PPPL	PPPL	PPP	pSer/pThr	Yes
		PAP	?	Yes
PPM	PPM	PPM	pSer/pThr	Yes
AP	AP	AP	pTyr, perhaps pSer/pThr	Yes
HP	HP	HP1	pTyr, pSer/pThr	Yes
		HP2	pTyr, small molecules	Yes
PHP	PHP	PHP	pHis	Yes
RTR1	RTR1	RTR1	pSer of CTD repeats	Yes

Synonymns: CC3 = Rhodanese; PPM = PP2C.

Abbreviations: CC1, Cysteine-based Class I; CC2, Cysteine-based Class II; CC3, Cysteine-based Class III; PPPL: PPP-like; PAP, Purple Acid Phosphatase; AP, Alkaline Phosphatase; HP, Histidine Phosphatase; HP1, Histidine Phosphatase, branch 1; HP2, Histidine Phosphatase, branch 2; CTD, RNA Poly II C-Terminal Domain.

Notes of classification

Phosphorylation of RNA polymerase II C-terminal domain

Both FCPs of HAD fold and SSU72 of CC2 fold can dephosphorylate CTD.

PTPLA is a dubious phosphatase

Notes on the PTPLA/PTP-like family that was claimed to be a phosphatase, but probably is not.

Non-protein phosphatases

Some phosphatases only dephosphorylate non-protein substrates, as far as known.

Technical notes

• What are the single-gene subfamilies in nine genomes. We keep them because they are found in at least two genera, although they are not found in the other genome among the nine genomes: dicty, budding yeast, monosiga, sponge, nematostella, C. elegans, Drosophila, sea urchin, and human.

References

1. Chen MJ, Dixon JE, and Manning G. Genomics and evolution of protein phosphatases. Sci Signal. 2017 Apr 11;10(474). DOI:10.1126/scisignal.aag1796 |