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.

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amoeba, and a few basal eukaryotes, but is absent from ecdysozoa (nematode and arthropoda), most fungi and monosiga (unpublished data, DUSP1, DUSP2, DUSP4, DUSP5).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, and may have other substrates.

DSP3 subfamily

DSP14 subfamily

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

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 It is found in most eukaryotes except fungi (unpublished data from gOrtholog).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

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

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 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

PTPMT1 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

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).