Phosphatase Family DSP

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. Based upon sequence similarity, domain combination and known functions, the subfamilies of DSP can be grouped as below.

Classification

DSP family consists of the subfamilies which 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 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amoeba, and a few basal eukaryotes, but is absent from ecdysozoa (nematode and arthropoda), most fungi and monosiga (unpublished data, DUSP1, DUSP2, DUSP4, DUSP5).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 consists of 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 consists of JNK/p38-selective MKPs, with two members in human, DUSP8 (hVH5) and DUSP16 (MKP-7). It is found in metazoa other than arthropods.

• DSP10 subfamily has a single member in human: DSP10 (MKP5). Similar to DSP8 subfamily, it is supposed to be JNK/p38 selective. It is found in most metazoa except nematodes.

• 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, and may have other substrates.

• DSP3 subfamily

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

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

• 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 It is found in most eukaryotes except fungi (unpublished data from gOrtholog).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 is a pseudophosphatase subfamily with a single human member. 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 has a single member in human, DUSP23. It is found in metazoan but lost in nematodes and most arthropods (unpublished data from gOrtholog). Its physiological substrate is unclear.

Other atypical DSPs

• DSP12 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 is mRNA capping enzyme found in holozoan. It has a phosphatase domain and guanylyltransferase.

• DSP11 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 is a glucan phosphatase, found in vertebrates and scattered other species. It has a single human member, EPM2A, mutations of which have been associated with myoclonic epilepsy of Lafora.

• PTPMT1 subfamily is a mitochondrial non-protein 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 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 consists of cell cycle genes widely found in eukaryotes with the exception of higher plants.

• CDKN3 (KAP) subfamily is a chordate-specific subfamily targeting threonine Cyclin-dependent kinases (CDKs) CDK1/CDC2 and CDK2. It is usually one copy per chordate genome.

• PTPDC1 subfamily (aka PTP9Q22) is found in holozoa and some protists, but lost from most insects. It may function in centriole and cilium biology.

Slingshot

• Slingshot subfamily, a subfamily conserved in holozoan but lost in nematodes, regulates cofilin phosphorylation with LIMKs and TESK kinases.