Difference between revisions of "Phosphatase Subfamily DSP15"
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=== Evolution === | === Evolution === | ||
| − | + | DSP15 subfamily is found across metazoan, even in amoebozoan and excavate, there are DSP15-like genes. It usually has a single copy in invertebrate genomes and two copies in vertebrate genomes, which indicated the subfamily emerged in metazoan and duplicated in vertebrates. | |
=== Domain === | === Domain === | ||
Revision as of 17:56, 5 March 2015
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP15
summary...
Evolution
DSP15 subfamily is found across metazoan, even in amoebozoan and excavate, there are DSP15-like genes. It usually has a single copy in invertebrate genomes and two copies in vertebrate genomes, which indicated the subfamily emerged in metazoan and duplicated in vertebrates.
Domain
DSP15 has a N-terminal myristoylation site and a phosphatase domain. The two members in human genome DUSP15 and DUSP22 are myristoylated at Gly-2. The myristoylation site targets the protein to plasma memrane. Mutation of the myristoylation site Gly-2 of DUSP15 abrogated membrane location [1].
Functions
Two human genes belong to this subfamily: DUSP15 and DUSP22.
DUSP15 (VHY)
Human DUSP15 is specifically expressed in testis [1] (also see GTEx portal). However, DUSP15 has also been reported to be transcriptionally regulated during oligodendrocyte differentiation and in multiple sclerosis lesions, in which DUSP15 dephosphorylates PDGFR-beta and SNX6 [2].
DUSP22 (VHX/JKAP/JSP1/LMW-DSP2)
Different from DUSP15, human DUSP22 is expressed in various tissues (see GTEx portal).
DUSP22 localizes in the actin filament-enriched region. Expression of DUSP22 reduced cell migration, whereas a DUSP22 mutant lacking catalytic activity promoted cell motility. DUSP22 dephosphorylates tyrosines 397, 576, and 577 of focal adhesion kinase (FAK) [3]. DUSP22 also dephosphorylates Ser-118 of estrogen receptor-alpha (ER-alpha) therefore regulating ER-alpha-mediated signaling [4].
Unexpectedly, DUSP22 is a positive rather than negative regulatory of JNK pathway. It did not interact with or dephosphorylate JNK in vitro, suggesting that DUSP22 exerts its effect on JNK in an indirect manner [5, 6].
DUSP22 may have other functions. It inhibits (may or may not by directly dephospho rylation) PKA activity and thereby determines TAU phosphorylation status and CREB signaling [7]. It also acts as a negative regulator (may or may not by directly dephospho rylation) of the IL-6/LIF/STAT3-mediated signaling pathway [8].
DUSP22 may represent a tumor-suppressor gene, since its loss may contribute to the pathogenesis of cutaneous anaplastic large-cell lymphomas (ALCLs) according to clinic cases [9].
References
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