Difference between revisions of "Phosphatase Family DSP"
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=== Subfamilies === | === Subfamilies === | ||
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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. These are named MKP, ('''M'''AP '''K'''inase '''P'''hosphatase). They are regulators of MAPK activity, and can mediate crosstalk between distinct MAPK pathways and between MAPK signalling and other intracellular signalling modules (see reviews <cite>Dickinson06, Caunt13</cite>). The rhodanese domains usually contain kinase-interacting motifs (KIMs) for MAPK binding <cite>Dickinson06</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. These are named MKP, ('''M'''AP '''K'''inase '''P'''hosphatase). They are regulators of MAPK activity, and can mediate crosstalk between distinct MAPK pathways and between MAPK signalling and other intracellular signalling modules (see reviews <cite>Dickinson06, Caunt13</cite>). The rhodanese domains usually contain kinase-interacting motifs (KIMs) for MAPK binding <cite>Dickinson06</cite>. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP1|DSP1]] ===== | |
| + | The DSP1 subfamily is an inducible nuclear MKP subfamily found throughout eukaryotes. As a key player in MAPK pathway, it is implicated in immune regulation and cancer. Human has four members, DUSP1 (MKP1), DUSP2, DUSP4 (MKP2) and DUSP5. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP6|DSP6]] ===== | |
| + | The DSP6 subfamily is a cytoplasmic MKP subfamily selectively dephoshorylating ERK. It is found throughout [[metazoa]] and duplicated in vertebrates. Human genome has three members: DUSP6 (MKP3/PYST1), DUSP7 (MKPX/PYST2) and DUSP9 (MKP4/PYST3). | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP8|DSP8]] ===== | |
| + | The DSP8 subfamily is a metazoan subfamily that functions as an MKP with preference towards JNK and p38. It is single copy in invertebrate but two copies in most vertebrates. The two human members DUSP8 and DUSP16 (MKP7) have different tissue expression patterns. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP10|DSP10]] ===== | |
| − | + | Human DUSP10 (MKP5) selectively dephosphorylates p38 and JNK. It is conserved across [[holozoa]] but lost in nematodes. Human DUSP10 is frequently dysregulated in colorectal cancer. | |
| − | + | ||
| + | ===== [[Phosphatase_Subfamily_STYXL1|STYXL1]] ===== | ||
| + | The STYXL1 subfamily is a pseudophosphatase (catalytically inactive) conserved in metazoa but lost in ecdysozoa. It is also known as MK-STYX, named after the catalytically inactive phosphatase subfamily [[Phosphatase_Subfamily_STYX|STYX]]. In comparison with STYX, it has an N-terminal rhodanese domain, which is a common feature between MKPs. Two binding partners have been known so far: phosphatase PTPMT1 and a Ras signaling regulator G3BP1. | ||
Some subfamilies of DSP family lack the rhodanese domain but function in similarly to MKPs. | Some subfamilies of DSP family lack the rhodanese domain but function in similarly to MKPs. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP3|DSP3]] ===== | |
| + | Human DSP3s are abundantly expressed in skeletal muscle and heart. It emerged in eumetazoan, lost in nematodes and duplicated in deuterostomia and vertebrates. Human has five members: DUSP3 (VHR), DUSP13 (BEDP/TMDP/MDSP/SKRP4), DUSP26 (MKP8), DUSP27, DUPD1. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP14|DSP14]] ===== | |
| + | The DSP14 subfamily emerged in eumetazoan and duplicated in vertebrates. Human has four members, DUSP14 (MKP6), DUSP18, DUSP21 and DUSP28 (VHP). Little is known about their functions. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP15|DSP15]] ===== | |
| + | The DSP15 subfamily emerged in metazoa and duplicated in vertebrates. It is characterized by a N-termnal myristoylation site which targets it to plasma membrane. Limited is known about its molecular function. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP19|DSP19]] ===== | |
| + | The DSP19 subfamily is widely found in eukaryotes but absent from fungi. Human DUSP19 (SKRP1) functions in the regulation of JNK signaling but the precise molecular mechanism is unclear. | ||
| − | + | ===== [[Phosphatase_Subfamily_STYX|STYX]] ===== | |
| − | + | The STYX subfamily is a catalytically inactive phosphatase found in most opisthokonts but lost in nematodes. | |
| − | + | ||
| + | ===== [[Phosphatase_Subfamily_DSP23|DSP23]] ===== | ||
| + | Human DUSP23 is a nuclear phosphatase found in metazoa but lost in ecdysozoa. | ||
Some subfamilies of DSP family dephosphorylate non-protein substrates: | Some subfamilies of DSP family dephosphorylate non-protein substrates: | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP12|DSP12]] ===== | |
| + | The DSP12 subfamily is found throughout unikonts, but its function is poorly understood. | ||
| − | + | ===== [[Phosphatase_Subfamily_RNGTT|RNGTT]] ===== | |
| + | The RNGTT subfamily is an mRNA capping enzyme found in [[holozoa]]. It has a phosphatase domain and guanylyltransferase. | ||
| − | + | ===== [[Phosphatase_Subfamily_DSP11|DSP11]] ===== | |
| + | The DSP11 subfamily is a metazoan-specific subfamily. Its physiological substrate is unknown, but several lines of evidence link this phosphatase to RNA splicing. Human has a single copy DUSP11 (PIR1). | ||
| − | + | ===== [[Phosphatase_Subfamily_Laforin|Laforin]] ===== | |
| − | + | The laforin subfamily is a glucan phosphatase, found in vertebrates and scattered other species. Mutations in the human member, EPM2A, are associated with myoclonic epilepsy of [http://en.wikipedia.org/wiki/Lafora_disease Lafora]. | |
| − | + | ||
| + | ===== [[Phosphatase_Subfamily_PTPMT1|PTPMT1]] ===== | ||
| + | The PTPMT1 subfamily is a mitochondrial non-protein phosphatase that converts phosphatidylglycerolphosphate (PGP) to phosphatidylglycerol, during 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. | ||
The subfamilies below are known or inferred to be cyclin-dependent kinase phosphatases: | The subfamilies below are known or inferred to be cyclin-dependent kinase phosphatases: | ||
| − | + | ===== [[Phosphatase_Subfamily_CDC14|CDC14]] ===== | |
| + | The CDC14 subfamily is a cell cycle genes widely found in eukaryotes with the exception of higher plants. | ||
| − | + | ===== [[Phosphatase_Subfamily_CDKN3|CDKN3]] ===== | |
| + | The CDKN3 (KAP) subfamily is a chordate-specific phosphatase targeting Cyclin-dependent kinases (CDKs) CDK1 and CDK2. | ||
| − | + | ===== [[Phosphatase_Subfamily_PTPDC1|PTPDC1]] ===== | |
| + | The PTPDC1 subfamily is found in [[holozoa]] and some protists, but lost from most insects. It may function in centriole and cilium biology. | ||
Lastly, PRL and Slingshot phosphatases: | Lastly, PRL and Slingshot phosphatases: | ||
| + | ===== [[Phosphatase_Subfamily_PRL|PRL]] ===== | ||
| + | The PRL (PTP4A) 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 unpublished data from gOrtholog]). The three human members, PRL1, PRL2, PRL3, have all been linked to cancer metastasis. | ||
| − | + | ===== [[Phosphatase_Subfamily_Slingshot|Slingshot]] ===== | |
| − | + | The slingshot subfamily is conserved in holozoan but lost in nematodes, regulates [http://en.wikipedia.org/wiki/Cofilin cofilin] phosphorylation in opposition to LIMK and TESK kinases. | |
| − | + | ||
=== References === | === References === | ||
Revision as of 02:52, 25 June 2015
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP
This family consists of the dual-specific protein phosphatases (DSPs) that dephosphorylate both tyrosine and serine/threonine, as well as related non-protein phosphatases.
Contents
Subfamilies
Several related subfamilies of DSP that dephosphorylate MAPK Kinases and share an N-terminal non-catalytic rhodanese domain. These are named MKP, (MAP Kinase Phosphatase). They are regulators of MAPK activity, and can mediate crosstalk between distinct MAPK pathways and between MAPK signalling and other intracellular signalling modules (see reviews [1, 2]). The rhodanese domains usually contain kinase-interacting motifs (KIMs) for MAPK binding [1].
DSP1
The DSP1 subfamily is an inducible nuclear MKP subfamily found throughout eukaryotes. As a key player in MAPK pathway, it is implicated in immune regulation and cancer. Human has four members, DUSP1 (MKP1), DUSP2, DUSP4 (MKP2) and DUSP5.
DSP6
The DSP6 subfamily is a cytoplasmic MKP subfamily selectively dephoshorylating ERK. It is found throughout metazoa and duplicated in vertebrates. Human genome has three members: DUSP6 (MKP3/PYST1), DUSP7 (MKPX/PYST2) and DUSP9 (MKP4/PYST3).
DSP8
The DSP8 subfamily is a metazoan subfamily that functions as an MKP with preference towards JNK and p38. It is single copy in invertebrate but two copies in most vertebrates. The two human members DUSP8 and DUSP16 (MKP7) have different tissue expression patterns.
DSP10
Human DUSP10 (MKP5) selectively dephosphorylates p38 and JNK. It is conserved across holozoa but lost in nematodes. Human DUSP10 is frequently dysregulated in colorectal cancer.
STYXL1
The STYXL1 subfamily is a pseudophosphatase (catalytically inactive) conserved in metazoa but lost in ecdysozoa. It is also known as MK-STYX, named after the catalytically inactive phosphatase subfamily STYX. In comparison with STYX, it has an N-terminal rhodanese domain, which is a common feature between MKPs. Two binding partners have been known so far: phosphatase PTPMT1 and a Ras signaling regulator G3BP1.
Some subfamilies of DSP family lack the rhodanese domain but function in similarly to MKPs.
DSP3
Human DSP3s are abundantly expressed in skeletal muscle and heart. It emerged in eumetazoan, lost in nematodes and duplicated in deuterostomia and vertebrates. Human has five members: DUSP3 (VHR), DUSP13 (BEDP/TMDP/MDSP/SKRP4), DUSP26 (MKP8), DUSP27, DUPD1.
DSP14
The DSP14 subfamily emerged in eumetazoan and duplicated in vertebrates. Human has four members, DUSP14 (MKP6), DUSP18, DUSP21 and DUSP28 (VHP). Little is known about their functions.
DSP15
The DSP15 subfamily emerged in metazoa and duplicated in vertebrates. It is characterized by a N-termnal myristoylation site which targets it to plasma membrane. Limited is known about its molecular function.
DSP19
The DSP19 subfamily is widely found in eukaryotes but absent from fungi. Human DUSP19 (SKRP1) functions in the regulation of JNK signaling but the precise molecular mechanism is unclear.
STYX
The STYX subfamily is a catalytically inactive phosphatase found in most opisthokonts but lost in nematodes.
DSP23
Human DUSP23 is a nuclear phosphatase found in metazoa but lost in ecdysozoa.
Some subfamilies of DSP family dephosphorylate non-protein substrates:
DSP12
The DSP12 subfamily is found throughout unikonts, but its function is poorly understood.
RNGTT
The RNGTT subfamily is an mRNA capping enzyme found in holozoa. It has a phosphatase domain and guanylyltransferase.
DSP11
The DSP11 subfamily is a metazoan-specific subfamily. Its physiological substrate is unknown, but several lines of evidence link this phosphatase to RNA splicing. Human has a single copy DUSP11 (PIR1).
Laforin
The laforin subfamily is a glucan phosphatase, found in vertebrates and scattered other species. Mutations in the human member, EPM2A, are associated with myoclonic epilepsy of Lafora.
PTPMT1
The PTPMT1 subfamily is a mitochondrial non-protein phosphatase that converts phosphatidylglycerolphosphate (PGP) to phosphatidylglycerol, during 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.
The subfamilies below are known or inferred to be cyclin-dependent kinase phosphatases:
CDC14
The CDC14 subfamily is a cell cycle genes widely found in eukaryotes with the exception of higher plants.
CDKN3
The CDKN3 (KAP) subfamily is a chordate-specific phosphatase targeting Cyclin-dependent kinases (CDKs) CDK1 and CDK2.
PTPDC1
The PTPDC1 subfamily is found in holozoa and some protists, but lost from most insects. It may function in centriole and cilium biology.
Lastly, PRL and Slingshot phosphatases:
PRL
The PRL (PTP4A) subfamily is present in animals, amoeba, and many basal eukaryotes, but is absent from fungi and plants (unpublished data from gOrtholog). The three human members, PRL1, PRL2, PRL3, have all been linked to cancer metastasis.
Slingshot
The slingshot subfamily is conserved in holozoan but lost in nematodes, regulates cofilin phosphorylation in opposition to LIMK and TESK kinases.
References
- Dickinson RJ and Keyse SM. Diverse physiological functions for dual-specificity MAP kinase phosphatases. J Cell Sci. 2006 Nov 15;119(Pt 22):4607-15. DOI:10.1242/jcs.03266 |
- Caunt CJ and Keyse SM. Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling. FEBS J. 2013 Jan;280(2):489-504. DOI:10.1111/j.1742-4658.2012.08716.x |
