View source for Phosphatase Subfamily DSP10

[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]:  [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_ DSP10 |Subfamily DSP10]] (MKP5)

Human DSP10 selectively dephosphorylates p38 and JNK. It is conserved across holozoan but lost in nematodes.

=== Evolution ===
The DSP10 (MKP5) subfamily is found in most [[holozoa]] except nematodes. DSP10 is usually one copy per genome, e.g. DUSP10 (MKP5) in human. Diptera lost rhodanese domain as inferred by BLASTing human against protein NR database of arthropods.

=== Domain ===
The DSP10 (MKP5) has two domains: rhodanese domain and phosphatase domain. The rhodanese domain can bind to kinases <cite>Tao07</cite>. Drosophila has lost the whole rhodanese domain.

=== Function ===
Human DUSP10 is a phosphatase specific for p38 and SAPK/JNK. It binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. p38 is a preferred substrate. It is present evenly in both the cytoplasm and the nucleus. DUSP10 is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli <cite>Tanoue99, Theodosiou99, Jeong06</cite>.

On the other hand, it has been reported that human DUSP10 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription <cite>Nomura12</cite>. 

Human DUSP10 is frequently upregulated in colorectal cancer (CRC). Certain mutations in DUSP10 correlate with the incidence of CRC. DUSP10/MKP5 also negatively regulates intestinal epithelial cell growth <cite>Png15</cite>.

Human DUSP10 (MKP5) is implicated in immune system. It functions in the type I interferon system responding to viral infection. It interacts with, dephosphorylates and inactivates [http://en.wikipedia.org/wiki/IRF3 Interferon regulatory factor 3 (IRF3)], an interferon regulatory factor which plays an important role in the type I interferon system. Increased type I interferon responses were observed in DUSP10/MKP5-deficient cells and animals upon various RNA virus infection, including H1N1 influenza virus, vesicular stomatitis virus and sendai virus <cite>James15</cite>. DUSP10/MKP5 also regulates adipose tissue inflammation and insulin resistance <cite>Zhang15</cite>.

=== Technical notes ===
===== Rhodanese domain lost in diptera =====
We observed the lost of rhodanese domain in Drosophila melanogaster. We then asked when the lose happened, it was lost in D. melanogaster only, or in all arthropods, or somewhere in between. We obtained all the DSP10s from our internal orthology database, searched the Pfam domains using Pfam web server (E-value cutoff 1.0), and eyeballed the presence and absence of rhodanese domain in 31 arthropods. We found the rhodanese domain was lost in diptera and is generally present in other arthropods.

=== References ===
<biblio>
#James15 pmid=25772359
#Jeong06 pmid=16806267
#Nomura12 pmid=22711061
#Png15 pmid=25772234
#Tanoue99 pmid=10391943
#Tao07 pmid=17400920
#Theodosiou99 pmid=10597297
#Zhang15 pmid=25922079
</biblio>