Difference between revisions of "Phosphatase Family DSP"

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(PTPMT1 subfamily)
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Several related subfamilies of DSP that dephosphorylate [http://kinase.com/wiki/index.php/Kinase_Family_MAPK MAPK Kinases] and share an N-terminal non-catalytic rhodanese domain.. As implied by its name, MKP is involved in [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase#Signalling_cascades MAPK signaling cascades]. The Rhodanese domains are regulatory and targeting, and include kinase-interacting motifs (KIMs) for MAPK binding <cite>keyse06</cite>.  
 
Several related subfamilies of DSP that dephosphorylate [http://kinase.com/wiki/index.php/Kinase_Family_MAPK MAPK Kinases] and share an N-terminal non-catalytic rhodanese domain.. As implied by its name, MKP is involved in [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase#Signalling_cascades MAPK signaling cascades]. The Rhodanese domains are regulatory and targeting, and include kinase-interacting motifs (KIMs) for MAPK binding <cite>keyse06</cite>.  
  
===== [[Subfamily_DSP1|DSP1 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP1|DSP1 subfamily]] =====
 
The subfamily is also known as inducible nuclear MKPs, which has four members in human, DUSP1 (MKP-1), DUSP2 (PAC-1), DUSP4 (MKP-2) and DUSP5 (hVH3).  The subfamily is found in animals, plants, amoeba, and a few basal eukaryotes, but is absent from ecdysozoa (nematode and arthropoda), most fungi and monosiga (unpublished data, [http://resdev.gene.com/gOrtholog/view/cluster/MC0008107/overview DUSP1], [http://resdev.gene.com/gOrtholog/view/cluster/MC0013833/overview DUSP2], [http://resdev.gene.com/gOrtholog/view/cluster/MC0006670/overview DUSP4], [http://resdev.gene.com/gOrtholog/view/cluster/MC0008873/overview DUSP5]).
 
The subfamily is also known as inducible nuclear MKPs, which has four members in human, DUSP1 (MKP-1), DUSP2 (PAC-1), DUSP4 (MKP-2) and DUSP5 (hVH3).  The subfamily is found in animals, plants, amoeba, and a few basal eukaryotes, but is absent from ecdysozoa (nematode and arthropoda), most fungi and monosiga (unpublished data, [http://resdev.gene.com/gOrtholog/view/cluster/MC0008107/overview DUSP1], [http://resdev.gene.com/gOrtholog/view/cluster/MC0013833/overview DUSP2], [http://resdev.gene.com/gOrtholog/view/cluster/MC0006670/overview DUSP4], [http://resdev.gene.com/gOrtholog/view/cluster/MC0008873/overview DUSP5]).
  
===== [[Subfamily_DSP6|DSP6 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP6|DSP6 subfamily]] =====
 
These are cytoplasmic ERK-specific MKPs, with three human members, DUSP6 (MKP-3), DUSP7 (MKP-X) and DUSP9 (MKP-4). The subfamily is found throughout metazoa.
 
These are cytoplasmic ERK-specific MKPs, with three human members, DUSP6 (MKP-3), DUSP7 (MKP-X) and DUSP9 (MKP-4). The subfamily is found throughout metazoa.
  
===== [[Subfamily_DSP8|DSP8 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP8|DSP8 subfamily]] =====
 
Jnk/p38-selective MKPs, with two members in human, DUSP8 (hVH5) and DUSP16 (MKP-7). Found in metazoa other than arthropods.
 
Jnk/p38-selective MKPs, with two members in human, DUSP8 (hVH5) and DUSP16 (MKP-7). Found in metazoa other than arthropods.
  
===== [[Subfamily_DSP10|DSP10 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP10|DSP10 subfamily]] =====
 
The only member in human is DSP10 (MKP5). Similar to DSP8 subfamily, it is supposed to be JNK/p38 selective. It is found in most metazoa except nematodes.
 
The only member in human is DSP10 (MKP5). Similar to DSP8 subfamily, it is supposed to be JNK/p38 selective. It is found in most metazoa except nematodes.
  
===== [[Subfamily_STYXL1|STYXL1 subfamily]] =====
+
===== [[Phosphatase_Subfamily_STYXL1|STYXL1 subfamily]] =====
 
STYXL1 subfamily is pseudophosphatase (catalytically inactive). It has a single member in human, STYXL1 (MK-STYX). It is found in metazoa but lost in ecdysozoa (arthropoda and nematoda).
 
STYXL1 subfamily is pseudophosphatase (catalytically inactive). It has a single member in human, STYXL1 (MK-STYX). It is found in metazoa but lost in ecdysozoa (arthropoda and nematoda).
  
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===== [[Phosphatase_Subfamily_DSP3|DSP3 subfamily]] =====
 
===== [[Phosphatase_Subfamily_DSP3|DSP3 subfamily]] =====
  
===== [[Subfamily_DSP14|DSP14 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP14|DSP14 subfamily]] =====
  
 
DSP14 subfamily has four members in human, DUSP14, DUSP18, DUSP21, DUSP28. It is found in eumetazoan.
 
DSP14 subfamily has four members in human, DUSP14, DUSP18, DUSP21, DUSP28. It is found in eumetazoan.
  
===== [[Subfamily_DSP15|DSP15 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP15|DSP15 subfamily]] =====
  
 
DSP15 subfamily has two members in human, DUSP15 and DUSP22. The subfamily is characterized by a N-terminal myristoylation site. It is found throughout metazoan ([http://resdev.gene.com/gOrtholog/view/cluster/MC0002932/overview see gOrtholog]).
 
DSP15 subfamily has two members in human, DUSP15 and DUSP22. The subfamily is characterized by a N-terminal myristoylation site. It is found throughout metazoan ([http://resdev.gene.com/gOrtholog/view/cluster/MC0002932/overview see gOrtholog]).
  
===== [[Subfamily_DSP19|DSP19 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP19|DSP19 subfamily]] =====
  
 
DSP19 subfamily has a single member in human DUSP19 (SKRP1). It is found in most eukaryotes except fungi ([http://resdev.gene.com/gOrtholog/view/cluster/MC0004288/overview unpublished data from gOrtholog]). DUSP19 appears to play a specific role in the regulation of jun-kinase (JNK) signaling; however, the precise mechanism by which it regulates this pathway remains controversial.
 
DSP19 subfamily has a single member in human DUSP19 (SKRP1). It is found in most eukaryotes except fungi ([http://resdev.gene.com/gOrtholog/view/cluster/MC0004288/overview unpublished data from gOrtholog]). DUSP19 appears to play a specific role in the regulation of jun-kinase (JNK) signaling; however, the precise mechanism by which it regulates this pathway remains controversial.
  
===== [[Subfamily_STYX|STYX subfamily]] =====
+
===== [[Phosphatase_Subfamily_STYX|STYX subfamily]] =====
  
 
STYX subfamily is pseudophosphatase. It has a single member in human STYX. STYX localizes to the nucleus, competes with DUSP4 for binding to ERK, and acts as a nuclear anchor that regulates ERK nuclear export <cite>farhan13</cite>. The subfamily is found in most opisthokonts but lost in nematodes. Although It is not found in Drosophila and budding yeast, it is found in other arthropoda and fungi ([http://resdev.gene.com/gOrtholog/view/cluster/MC0005385/overview unpublished data from gOrtholog]).
 
STYX subfamily is pseudophosphatase. It has a single member in human STYX. STYX localizes to the nucleus, competes with DUSP4 for binding to ERK, and acts as a nuclear anchor that regulates ERK nuclear export <cite>farhan13</cite>. The subfamily is found in most opisthokonts but lost in nematodes. Although It is not found in Drosophila and budding yeast, it is found in other arthropoda and fungi ([http://resdev.gene.com/gOrtholog/view/cluster/MC0005385/overview unpublished data from gOrtholog]).
  
===== [[Subfamily_DSP23|DSP23 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP23|DSP23 subfamily]] =====
  
 
DSP23 subfamily has a single member in human, DUSP23. It is found in metazoan but lost in nematodes and most arthropoda ([http://resdev.gene.com/gOrtholog/view/cluster/MC0006453/overview unpublished data from gOrtholog]). Its physiological substrate is unclear.
 
DSP23 subfamily has a single member in human, DUSP23. It is found in metazoan but lost in nematodes and most arthropoda ([http://resdev.gene.com/gOrtholog/view/cluster/MC0006453/overview unpublished data from gOrtholog]). Its physiological substrate is unclear.
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==== Other ''atypical'' DSPs  ====
 
==== Other ''atypical'' DSPs  ====
  
===== [[Subfamily_DSP12|DSP12 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP12|DSP12 subfamily]] =====
 
The subfamily is conserved throughout unikonts and usually a single copy in each genome. The human DUSP12 is localized primarily in the nucleus and is involved in glucokinase regulation. The yeast ortholog [http://www.yeastgenome.org/cgi-bin/locus.fpl?locus=YIR026c YHV1] is a tyrosine-specific protein phosphatase associates with pre-60S ribosome.
 
The subfamily is conserved throughout unikonts and usually a single copy in each genome. The human DUSP12 is localized primarily in the nucleus and is involved in glucokinase regulation. The yeast ortholog [http://www.yeastgenome.org/cgi-bin/locus.fpl?locus=YIR026c YHV1] is a tyrosine-specific protein phosphatase associates with pre-60S ribosome.
  
  
===== [[Subfamily_RNGTT|RNGTT subfamily]] =====
+
===== [[Phosphatase_Subfamily_RNGTT|RNGTT subfamily]] =====
  
 
RNGTT is RNA guanylyltransferase and 5'-phosphatase. Besides phosphatase domain, it has mRNA capping enzyme domain. It is ubiquitous in eukaryotes and usually there is a single copy in each organism ([http://resdev.gene.com/gOrtholog/view/cluster/MC0005385/overview unpublished data from gOrtholog]).
 
RNGTT is RNA guanylyltransferase and 5'-phosphatase. Besides phosphatase domain, it has mRNA capping enzyme domain. It is ubiquitous in eukaryotes and usually there is a single copy in each organism ([http://resdev.gene.com/gOrtholog/view/cluster/MC0005385/overview unpublished data from gOrtholog]).
  
===== [[Subfamily_DSP11|DSP11 subfamily]] =====
+
===== [[Phosphatase_Subfamily_DSP11|DSP11 subfamily]] =====
  
 
DSP subfamily has a single member in human, DUSP11 (PIR1). Its exact physiological substrate is unknown, but several lines of evidence link this phosphatase to RNA splicing. This is not surprising given that it is close to another ''atypical'' DSP, RNGTT, RNA guanylyltransferase and 5'-phosphatase. DSP11 subfamily is found through metazoan ([http://resdev.gene.com/gOrtholog/view/cluster/MC0004984/overview unpublished data from gOrtholog]).
 
DSP subfamily has a single member in human, DUSP11 (PIR1). Its exact physiological substrate is unknown, but several lines of evidence link this phosphatase to RNA splicing. This is not surprising given that it is close to another ''atypical'' DSP, RNGTT, RNA guanylyltransferase and 5'-phosphatase. DSP11 subfamily is found through metazoan ([http://resdev.gene.com/gOrtholog/view/cluster/MC0004984/overview unpublished data from gOrtholog]).
  
===== [[Subfamily_Laforin|Laforin subfamily]] =====
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===== [[Phosphatase_Subfamily_Laforin|Laforin subfamily]] =====
  
 
Laforin subfamily has a single copy in human, EPM2A. As implied by its name, mutations in this gene have been associated with myoclonic epilepsy of [http://en.wikipedia.org/wiki/Lafora_disease Lafora]. Laforin subfamily is mostly found in vertebrates. It is characterized by a carbohydrate-binding domain. It is supposed to dephosphorylate glycogen.
 
Laforin subfamily has a single copy in human, EPM2A. As implied by its name, mutations in this gene have been associated with myoclonic epilepsy of [http://en.wikipedia.org/wiki/Lafora_disease Lafora]. Laforin subfamily is mostly found in vertebrates. It is characterized by a carbohydrate-binding domain. It is supposed to dephosphorylate glycogen.
  
===== [[PTPMT1|PTPMT1 subfamily]] =====
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===== [[Phosphatase_Subfamily_PTPMT1|PTPMT1 subfamily]] =====
 
PTPMT1 is a mitochondrial phosphatase that converts phosphatidylglycerolphosphate (PGP) to phosphatidylglycerol, during ''de novo'' biosynthesis of cardiolipin. It is found in most or all animals and higher plants, and most protists but is absent from fungi, ''Monosiga'', and some lower plants.
 
PTPMT1 is a mitochondrial phosphatase that converts phosphatidylglycerolphosphate (PGP) to phosphatidylglycerol, during ''de novo'' biosynthesis of cardiolipin. It is found in most or all animals and higher plants, and most protists but is absent from fungi, ''Monosiga'', and some lower plants.
  
 
==== PRL ====
 
==== PRL ====
  
===== [[Subfamily_PRL|PRL subfamily]] =====
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===== [[Phosphatase_Subfamily_PRL|PRL subfamily]] =====
 
PRL is short for Phosphatases of Regenerating Liver. There are three PRLs in human, PRL1, PRL2, PRL3, all of which have been identified as key contributors to metastasis in several human cancers. PRL subfamily is present in animals, amoeba, and many basal eukaryotes, but is absent from fungi and plants ([http://resdev.gene.com/gOrtholog/view/cluster/MC0001030/overview unpublish data from gOrtholog]).  [[Subfamily_PRL|Read more]].
 
PRL is short for Phosphatases of Regenerating Liver. There are three PRLs in human, PRL1, PRL2, PRL3, all of which have been identified as key contributors to metastasis in several human cancers. PRL subfamily is present in animals, amoeba, and many basal eukaryotes, but is absent from fungi and plants ([http://resdev.gene.com/gOrtholog/view/cluster/MC0001030/overview unpublish data from gOrtholog]).  [[Subfamily_PRL|Read more]].
  
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The subfamilies below are known as or supposed to be cyclin-dependent kinase phosphatase.
 
The subfamilies below are known as or supposed to be cyclin-dependent kinase phosphatase.
  
===== [[Subfamily_CDC14|CDC14 subfamily]] =====
+
===== [[Phosphatase_Subfamily_CDC14|CDC14 subfamily]] =====
  
 
CDC14 subfamily is found throughout eukaryotes ([http://resdev.gene.com/gOrtholog/view/cluster/MC0000760/overview unpublished data from gOrtholog]), but may have different functions <cite>schiebel10</cite>. It has three copies in human, CDC14A, CDC14B and CDC14C.
 
CDC14 subfamily is found throughout eukaryotes ([http://resdev.gene.com/gOrtholog/view/cluster/MC0000760/overview unpublished data from gOrtholog]), but may have different functions <cite>schiebel10</cite>. It has three copies in human, CDC14A, CDC14B and CDC14C.
  
===== [[Subfamily_CDKN3|CDKN3 subfamily]] =====
+
===== [[Phosphatase_Subfamily_CDKN3|CDKN3 subfamily]] =====
 
CDKN3 subfamily is found in vertebrates, usually one copy per organism. Human CDKN3 inhibits cyclin-dependent kinase (CDK) by interacting with and dephosphorylating CDK2 kinase.
 
CDKN3 subfamily is found in vertebrates, usually one copy per organism. Human CDKN3 inhibits cyclin-dependent kinase (CDK) by interacting with and dephosphorylating CDK2 kinase.
  
===== [[Subfamily_PTPDC1|PTPDC1 subfamily]] =====
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===== [[Phosphatase_Subfamily_PTPDC1|PTPDC1 subfamily]] =====
 
PTPDC1 (aka PTP9Q22) is found in holozoa (monosiga + metazoa) and excavata. It is absent from most of arthropoda. It is function is unclear. Human PTPDC1 has a C-terminal region to the predicted phosphatase catalytic domain.
 
PTPDC1 (aka PTP9Q22) is found in holozoa (monosiga + metazoa) and excavata. It is absent from most of arthropoda. It is function is unclear. Human PTPDC1 has a C-terminal region to the predicted phosphatase catalytic domain.
  
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==== Slingshot ====
 
==== Slingshot ====
  
===== [[Subfamily_Slingshot|Slingshot subfamily]] =====
+
===== [[Phosphatase_Subfamily_Slingshot|Slingshot subfamily]] =====
  
 
Slingshot subfamily consists for three genes in human, SSH1, SSH2, SSH3. Slingshot phosphatases dephosphorylates [http://en.wikipedia.org/wiki/Actin-Depolymerizing_Factor ADF] and [http://en.wikipedia.org/wiki/Cofilin cofilin], and thus suppresses actin filament assembly induced by the kinases TESK1 (testis-specific kinase 1) and LIMK1 (LIM domain kinase 1). Slingshot subfamily is most likely to emerge in holozoan (monosiga + metazoan).
 
Slingshot subfamily consists for three genes in human, SSH1, SSH2, SSH3. Slingshot phosphatases dephosphorylates [http://en.wikipedia.org/wiki/Actin-Depolymerizing_Factor ADF] and [http://en.wikipedia.org/wiki/Cofilin cofilin], and thus suppresses actin filament assembly induced by the kinases TESK1 (testis-specific kinase 1) and LIMK1 (LIM domain kinase 1). Slingshot subfamily is most likely to emerge in holozoan (monosiga + metazoan).

Revision as of 01:20, 28 December 2014

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP

This family consists of the dual-specific protein phosphatases (DSPs). Not all so-called DSPs are protein phosphatases. For instance, PTPMT1 is phosphatidylglycerolphosphate phosphatase, Laforin is glucan phosphatase. Based upon sequence similarity, domain combination and known functions, the subfamilies of DSP can be grouped as below.


MAP Kinase Phosphatase (MKP)

Several related subfamilies of DSP that dephosphorylate MAPK Kinases and share an N-terminal non-catalytic rhodanese domain.. As implied by its name, MKP is involved in MAPK signaling cascades. The Rhodanese domains are regulatory and targeting, and include kinase-interacting motifs (KIMs) for MAPK binding [1].

DSP1 subfamily

The subfamily is also known as inducible nuclear MKPs, which has four members in human, DUSP1 (MKP-1), DUSP2 (PAC-1), DUSP4 (MKP-2) and DUSP5 (hVH3). The subfamily is found in animals, plants, amoeba, and a few basal eukaryotes, but is absent from ecdysozoa (nematode and arthropoda), most fungi and monosiga (unpublished data, DUSP1, DUSP2, DUSP4, DUSP5).

DSP6 subfamily

These are cytoplasmic ERK-specific MKPs, with three human members, DUSP6 (MKP-3), DUSP7 (MKP-X) and DUSP9 (MKP-4). The subfamily is found throughout metazoa.

DSP8 subfamily

Jnk/p38-selective MKPs, with two members in human, DUSP8 (hVH5) and DUSP16 (MKP-7). Found in metazoa other than arthropods.

DSP10 subfamily

The only member in human is DSP10 (MKP5). Similar to DSP8 subfamily, it is supposed to be JNK/p38 selective. It is found in most metazoa except nematodes.

STYXL1 subfamily

STYXL1 subfamily is pseudophosphatase (catalytically inactive). It has a single member in human, STYXL1 (MK-STYX). It is found in metazoa but lost in ecdysozoa (arthropoda and nematoda).

Atypical DSPs that may act as MKPs

Here, Atypical generally means these DSPs lack rhodanese domain found in MKPs. Some of these Atypical DSPs are MAPK phosphatases, although they do not have rhodanese domain (perhaps, they harbor kinase-interacting motif somewhere else instead of within rhodanese domain). In general, Atypical DSPs have various physiological substrates.

DSP3 subfamily
DSP14 subfamily

DSP14 subfamily has four members in human, DUSP14, DUSP18, DUSP21, DUSP28. It is found in eumetazoan.

DSP15 subfamily

DSP15 subfamily has two members in human, DUSP15 and DUSP22. The subfamily is characterized by a N-terminal myristoylation site. It is found throughout metazoan (see gOrtholog).

DSP19 subfamily

DSP19 subfamily has a single member in human DUSP19 (SKRP1). It is found in most eukaryotes except fungi (unpublished data from gOrtholog). DUSP19 appears to play a specific role in the regulation of jun-kinase (JNK) signaling; however, the precise mechanism by which it regulates this pathway remains controversial.

STYX subfamily

STYX subfamily is pseudophosphatase. It has a single member in human STYX. STYX localizes to the nucleus, competes with DUSP4 for binding to ERK, and acts as a nuclear anchor that regulates ERK nuclear export [2]. The subfamily is found in most opisthokonts but lost in nematodes. Although It is not found in Drosophila and budding yeast, it is found in other arthropoda and fungi (unpublished data from gOrtholog).

DSP23 subfamily

DSP23 subfamily has a single member in human, DUSP23. It is found in metazoan but lost in nematodes and most arthropoda (unpublished data from gOrtholog). Its physiological substrate is unclear.


Other atypical DSPs

DSP12 subfamily

The subfamily is conserved throughout unikonts and usually a single copy in each genome. The human DUSP12 is localized primarily in the nucleus and is involved in glucokinase regulation. The yeast ortholog YHV1 is a tyrosine-specific protein phosphatase associates with pre-60S ribosome.


RNGTT subfamily

RNGTT is RNA guanylyltransferase and 5'-phosphatase. Besides phosphatase domain, it has mRNA capping enzyme domain. It is ubiquitous in eukaryotes and usually there is a single copy in each organism (unpublished data from gOrtholog).

DSP11 subfamily

DSP subfamily has a single member in human, DUSP11 (PIR1). Its exact physiological substrate is unknown, but several lines of evidence link this phosphatase to RNA splicing. This is not surprising given that it is close to another atypical DSP, RNGTT, RNA guanylyltransferase and 5'-phosphatase. DSP11 subfamily is found through metazoan (unpublished data from gOrtholog).

Laforin subfamily

Laforin subfamily has a single copy in human, EPM2A. As implied by its name, mutations in this gene have been associated with myoclonic epilepsy of Lafora. Laforin subfamily is mostly found in vertebrates. It is characterized by a carbohydrate-binding domain. It is supposed to dephosphorylate glycogen.

PTPMT1 subfamily

PTPMT1 is a mitochondrial phosphatase that converts phosphatidylglycerolphosphate (PGP) to phosphatidylglycerol, during de novo biosynthesis of cardiolipin. It is found in most or all animals and higher plants, and most protists but is absent from fungi, Monosiga, and some lower plants.

PRL

PRL subfamily

PRL is short for Phosphatases of Regenerating Liver. There are three PRLs in human, PRL1, PRL2, PRL3, all of which have been identified as key contributors to metastasis in several human cancers. PRL subfamily is present in animals, amoeba, and many basal eukaryotes, but is absent from fungi and plants (unpublish data from gOrtholog). Read more.


CDK phosphatases

The subfamilies below are known as or supposed to be cyclin-dependent kinase phosphatase.

CDC14 subfamily

CDC14 subfamily is found throughout eukaryotes (unpublished data from gOrtholog), but may have different functions [3]. It has three copies in human, CDC14A, CDC14B and CDC14C.

CDKN3 subfamily

CDKN3 subfamily is found in vertebrates, usually one copy per organism. Human CDKN3 inhibits cyclin-dependent kinase (CDK) by interacting with and dephosphorylating CDK2 kinase.

PTPDC1 subfamily

PTPDC1 (aka PTP9Q22) is found in holozoa (monosiga + metazoa) and excavata. It is absent from most of arthropoda. It is function is unclear. Human PTPDC1 has a C-terminal region to the predicted phosphatase catalytic domain.


Slingshot

Slingshot subfamily

Slingshot subfamily consists for three genes in human, SSH1, SSH2, SSH3. Slingshot phosphatases dephosphorylates ADF and cofilin, and thus suppresses actin filament assembly induced by the kinases TESK1 (testis-specific kinase 1) and LIMK1 (LIM domain kinase 1). Slingshot subfamily is most likely to emerge in holozoan (monosiga + metazoan).