Difference between revisions of "Phosphatase classification"

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Phosphatases were first clustered by sequence similarity in the phosphatase domain, and additional information from domains outside of the catalytic domain, from evolutionary conservation, and from known functions was added. The result is a hybrid classification, in which no criterion is universally satisfied, but aims to be of practical use to a range of phosphatase interests. The classification grows as new phosphatomes are sequenced.  
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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 <cite>Chen</cite>.
  
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== Classification Chart ==
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== Classification Chart of Protein Phosphatases ==
  
 
{| class="wikitable" border="2" style="background: #ffffff; border: 1px #000000 solid; border-collapse: collapse; font-size: 100%;" cellpadding="5" cellspacing="10"
 
{| class="wikitable" border="2" style="background: #ffffff; border: 1px #000000 solid; border-collapse: collapse; font-size: 100%;" cellpadding="5" cellspacing="10"
 
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!bgcolor="#ffffff" rowspan="1" align="center" |Superfamily|| bgcolor="#ffffff" colspan="1" align="center" |Family|| bgcolor="#ffffff" colspan="1" align="center"| Substrate|| bgcolor="#ffffff" colspan="1" align="center"| Present in human
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!bgcolor="#ffffff" rowspan="1" |Fold||bgcolor="#ffffff" rowspan="1" |Superfamily|| bgcolor="#ffffff" colspan="1" |Family|| bgcolor="#ffffff" colspan="1" | Substrate|| bgcolor="#ffffff" colspan="1" | Present in human
 
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|-
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|bgcolor="#ffffff" rowspan="4" align="center" |[[Phosphatase_Superfamily_Cys-based_I|Cys-based Group I]]|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_HMWPTP|Classic PTP]]|| bgcolor="#ffffff" colspan="1" align="center"| pTyr || bgcolor="#ffffff" colspan="1" align="center"| Yes
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|bgcolor="#ffffff" rowspan="7" | [[Phosphatase_Fold_CC1|CC1]]||bgcolor="#ffffff" rowspan="7" | [[Phosphatase_Superfamily_CC1|CC1]] || bgcolor="#ffffff" colspan="1" | [[Phosphatase_Family_PTP|PTP]]|| bgcolor="#ffffff" colspan="1" | pTyr || bgcolor="#ffffff" colspan="1" | Yes
 
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| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_DSP_PTEN|DSP and PTEN]]|| bgcolor="#ffffff" colspan="1" align="center"| pTyr, pSer/pThr, lipid || bgcolor="#ffffff" colspan="1" align="center"| Yes
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_DSP|DSP]]|| bgcolor="#ffffff" colspan="1" | pTyr, pSer/pThr, small molecule || bgcolor="#ffffff" colspan="1" | Yes
 
|-
 
|-
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| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_Myotubularin|Myotubularin]]|| bgcolor="#ffffff" colspan="1" align="center"| lipid || bgcolor="#ffffff" colspan="1" align="center"| Yes
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_PTEN|PTEN]]|| bgcolor="#ffffff" colspan="1" | lipid || bgcolor="#ffffff" colspan="1" | Yes
 
|-
 
|-
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| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_OCA|OCA]]|| bgcolor="#ffffff" colspan="1" align="center"| ? || bgcolor="#ffffff" colspan="1" align="center"| No
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_Myotubularin|Myotubularin]]|| bgcolor="#ffffff" colspan="1" | lipid || bgcolor="#ffffff" colspan="1" | Yes
 
|-
 
|-
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|bgcolor="#ffffff" rowspan="1" align="center" |[[Phosphatase_Superfamily_Cys-based_II|Cys-based Group II]] (Rhondanese)|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_CDC25|CDC25]]|| bgcolor="#ffffff" colspan="1" align="center"| pTyr, pThr || bgcolor="#ffffff" colspan="1" align="center"| Yes
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_Sac|SAC]]|| bgcolor="#ffffff" colspan="1" | lipid || bgcolor="#ffffff" colspan="1" | Yes
 
|-
 
|-
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|bgcolor="#ffffff" rowspan="3" align="center" |[[Phosphatase_Superfamily_Cys-based_III|Cys-based Group III]]|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_LMWPTP|LMWPTP]]|| bgcolor="#ffffff" colspan="1" align="center"| pTyr || bgcolor="#ffffff" colspan="1" align="center"| Yes
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_Paladin|Paladin]]|| bgcolor="#ffffff" colspan="1" | inactive || bgcolor="#ffffff" colspan="1" | Yes
 
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|-
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| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_SSU72|SSU72]]|| bgcolor="#ffffff" colspan="1" align="center"| pSer || bgcolor="#ffffff" colspan="1" align="center"| Yes
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_OCA|OCA]]|| bgcolor="#ffffff" colspan="1" | ? || bgcolor="#ffffff" colspan="1" | No
 
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| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_ArsC|ArsC]]|| bgcolor="#ffffff" colspan="1" align="center"| Arsenate || bgcolor="#ffffff" colspan="1" align="center"| No
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|bgcolor="#ffffff" rowspan="3" |[[Phosphatase_Fold_CC2|CC2]]||bgcolor="#ffffff" rowspan="3" |[[Phosphatase_Superfamily_CC2|CC2]] || bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_LMWPTP|LMWPTP]]|| bgcolor="#ffffff" colspan="1" | pTyr || bgcolor="#ffffff" colspan="1" | Yes
 
|-
 
|-
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|bgcolor="#ffffff" rowspan="4" align="center" |[[Phosphatase_Group_HAD|HAD]]|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_EYA|EYA]]|| bgcolor="#ffffff" colspan="1" align="center"| pTyr || bgcolor="#ffffff" colspan="1" align="center"| Yes
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_SSU72|SSU72]]|| bgcolor="#ffffff" colspan="1" | pSer || bgcolor="#ffffff" colspan="1" | Yes
 
|-
 
|-
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|bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_FCP|FCP]]|| bgcolor="#ffffff" colspan="1" align="center"| pSer || bgcolor="#ffffff" colspan="1" align="center"| Yes
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| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_ArsC|ArsC]]|| bgcolor="#ffffff" colspan="1" | Arsenate || bgcolor="#ffffff" colspan="1" | No
 
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|bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_NagD|NagD]]|| bgcolor="#ffffff" colspan="1" align="center"| pTyr, pSer || bgcolor="#ffffff" colspan="1" align="center"| Yes
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|bgcolor="#ffffff" rowspan="1" |[[Phosphatase_Fold_Rhodanese|CC3]]||bgcolor="#ffffff" rowspan="1" |[[Phosphatase_Superfamily_CC3|CC3]]|| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_CDC25|CDC25]]|| bgcolor="#ffffff" colspan="1" | pTyr, pThr || bgcolor="#ffffff" colspan="1" | Yes
 
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|-
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|bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_MDP1|MDP1]]|| bgcolor="#ffffff" colspan="1" align="center"| pTyr? || bgcolor="#ffffff" colspan="1" align="center"| Yes
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|bgcolor="#ffffff" rowspan="3" |[[Phosphatase_Fold_HAD|HAD]]||bgcolor="#ffffff" rowspan="3" |[[Phosphatase_Superfamily_HAD|HAD]]|| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_EYA|EYA]]|| bgcolor="#ffffff" colspan="1" | pTyr || bgcolor="#ffffff" colspan="1" | Yes
 
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|bgcolor="#ffffff" rowspan="1" align="center" |[[Phosphatase_Superfamily_PPP|Metallo-dependent phosphatases]]|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_PPP|PPP]]|| bgcolor="#ffffff" colspan="1" align="center"| pSer/pThr || bgcolor="#ffffff" colspan="1" align="center"| Yes
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|bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_FCP|FCP]]|| bgcolor="#ffffff" colspan="1" | pSer || bgcolor="#ffffff" colspan="1" | Yes
 
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|bgcolor="#ffffff" rowspan="1" align="center" |[[Phosphatase_Superfamily_PPM|PPM]] (a.k.a. PP2C)|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_PPM|PPM]]|| bgcolor="#ffffff" colspan="1" align="center"| pSer/pThr || bgcolor="#ffffff" colspan="1" align="center"| Yes
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|bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_NagD|NagD]]|| bgcolor="#ffffff" colspan="1" | pTyr, pSer || bgcolor="#ffffff" colspan="1" | Yes
 
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|-
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|bgcolor="#ffffff" rowspan="1" align="center" |[[Phosphatase_Superfamily_PHP|PHP]]|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_PHP|PHP]]|| bgcolor="#ffffff" colspan="1" align="center"| pHis || bgcolor="#ffffff" colspan="1" align="center"| Yes
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|bgcolor="#ffffff" rowspan="2"  |[[Phosphatase_Fold_PPPL|PPPL]]||bgcolor="#ffffff" rowspan="2" |[[Phosphatase_Superfamily_PPPL|PPPL]] || bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_PPP|PPP]]|| bgcolor="#ffffff" colspan="1" | pSer/pThr || bgcolor="#ffffff" colspan="1" | Yes
 
|-
 
|-
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|bgcolor="#ffffff" rowspan="1" align="center" |[[Phosphatase_Superfamily_RTR1|RTR1]]|| bgcolor="#ffffff" colspan="1" align="center" |[[Phosphatase_Family_RTR1|RTR1]]|| bgcolor="#ffffff" colspan="1" align="center"| pSer || bgcolor="#ffffff" colspan="1" align="center"| Yes
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|bgcolor="#ffffff" colspan="1"  |[[Phosphatase_Family_PAP|PAP]] || bgcolor="#ffffff" colspan="1" | ? || bgcolor="#ffffff" colspan="1" | Yes
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|-
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|bgcolor="#ffffff" rowspan="1" |[[Phosphatase_Fold_PPM|PPM]]||bgcolor="#ffffff" rowspan="1" |[[Phosphatase_Superfamily_PPM|PPM]]|| bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_PPM|PPM]]|| bgcolor="#ffffff" colspan="1" | pSer/pThr || bgcolor="#ffffff" colspan="1" | Yes
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|-
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|bgcolor="#ffffff" rowspan="1"  |[[Phosphatase_Fold_AP|AP]]||bgcolor="#ffffff" rowspan="1"  |[[Phosphatase_Superfamily_AP|AP]] || bgcolor="#ffffff" colspan="1" |[[Phosphatase_Family_AP|AP]]|| bgcolor="#ffffff" colspan="1" | pTyr, perhaps pSer/pThr || bgcolor="#ffffff" colspan="1" | Yes
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|-
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|bgcolor="#ffffff" rowspan="2"  |[[Phosphatase_Fold_HP|HP]]||bgcolor="#ffffff" rowspan="2"  |[[Phosphatase_Superfamily_HP|HP]] || bgcolor="#ffffff" colspan="1"  |[[Phosphatase_Family_HP1|HP1]]|| bgcolor="#ffffff" colspan="1" | pTyr, pSer/pThr || bgcolor="#ffffff" colspan="1" | Yes
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|-
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| bgcolor="#ffffff" colspan="1"  |[[Phosphatase_Family_HP2|HP2]]|| bgcolor="#ffffff" colspan="1" | pTyr, small molecules || bgcolor="#ffffff" colspan="1" | Yes
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|-
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|bgcolor="#ffffff" rowspan="1"  |[[Phosphatase_Fold_PHP|PHP]]||bgcolor="#ffffff" rowspan="1"  |[[Phosphatase_Superfamily_PHP|PHP]]|| bgcolor="#ffffff" colspan="1"  |[[Phosphatase_Family_PHP|PHP]]|| bgcolor="#ffffff" colspan="1" | pHis || bgcolor="#ffffff" colspan="1" | Yes
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|-
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|bgcolor="#ffffff" rowspan="1"  |[[Phosphatase_Fold_RTR1|RTR1]]||bgcolor="#ffffff" rowspan="1"  |[[Phosphatase_Superfamily_RTR1|RTR1]]|| bgcolor="#ffffff" colspan="1"  |[[Phosphatase_Family_RTR1|RTR1]]|| bgcolor="#ffffff" colspan="1" | pSer of CTD repeats || bgcolor="#ffffff" colspan="1" | Yes
 
|}
 
|}
  
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== [[other_phosphatase|Other Phosphatases]] ==
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Synonymns: CC3 = Rhodanese; PPM = PP2C.
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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.
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=== Notes of classification ===
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===== [[CTD_Phosphorylation|Phosphorylation of RNA polymerase II C-terminal domain]] =====
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Both FCPs of HAD fold and SSU72 of CC2 fold can dephosphorylate CTD.
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===== [[PTPLA|PTPLA is a dubious phosphatase]] =====
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Notes on the PTPLA/PTP-like family that was claimed to be a phosphatase, but probably is not.
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===== [[Non-protein_phosphatases|Non-protein phosphatases]] =====
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Some phosphatases only dephosphorylate non-protein substrates, as far as known.
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===== [[Other_Classification_Schemes|Other Classification Schemes]] =====
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=== Technical notes ===
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* What are the [[Single-Gene_Subfamilies_in_Nine_Genomes|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.
  
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== [[Other_Classification_Schemes|Other Classification Schemes]] ==
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===References===
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<biblio>
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#Chen pmid=28400531
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</biblio>

Latest revision as of 23:51, 13 April 2017

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.

Other Classification Schemes

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 | PubMed ID:28400531 | HubMed [Chen]
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