Difference between revisions of "Phosphatase Subfamily DSP1"
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[[Phosphatase classification|Phosphatase Classification]]: Superfamily [[Phosphatase_Superfamily_CC1|CC1]]: Family [[Phosphatase_Family_DSP|DSP]]: [[Phosphatase_Subfamily_DSP1|Subfamily DSP1]] | [[Phosphatase classification|Phosphatase Classification]]: Superfamily [[Phosphatase_Superfamily_CC1|CC1]]: Family [[Phosphatase_Family_DSP|DSP]]: [[Phosphatase_Subfamily_DSP1|Subfamily DSP1]] | ||
| − | + | summary.... | |
| − | + | ||
| − | + | ||
===Evolution=== | ===Evolution=== | ||
| − | + | DSP1 subfamily is widely found across eukaryotes. It is present in animals, plants, amoeba, and some basal eukaryotes, but is absent from ecdysozoa (nematodes and arthropods), most fungi and monosiga (unpublished data, [http://resdev.gene.com/gOrtholog/view/cluster/MC0008107/overview DUSP1], [http://resdev.gene.com/gOrtholog/view/cluster/MC0013833/overview DUSP2], [http://resdev.gene.com/gOrtholog/view/cluster/MC0006670/overview DUSP4], [http://resdev.gene.com/gOrtholog/view/cluster/MC0008873/overview DUSP5]). | |
===Domain Structure=== | ===Domain Structure=== | ||
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===Functions=== | ===Functions=== | ||
| + | In general, DSP1 are inducible nuclear MAP Kinase phosphatases (MKPs), also known as the Group A DSPs. Human members are DUSP1, DUSP2, DUSP4 and DUSP5. Their substrate specificity, subcellular localization and etc have been summarized in Table 1 in review paper <cite>Patterson09</cite>. | ||
| + | |||
| + | ====== DUSP1 (MKP1/hVH1) ====== | ||
| + | DUSP1 is the best characterized phosphatase within this subfamily. It prefers to dephosphorylates p38 and JNK over ERK. DUSP1 is involved in immune regulation and cancer. DUSP1 is an important negative-feedback regulator of macrophage function and the inflammatory response to TLR signalling, and plays key regulatory roles in both innate and adaptive immune responses via inactivation of p38 and JNK (reviewed in <cite>Patterson09</cite>). It is worthy pointing out that DUSP1 expression is strictly regulated in brain (see [http://www.gtexportal.org/home/gene/DUSP1 GTEx]). | ||
| + | |||
| + | (PS: more reading is needed). | ||
| + | |||
| + | ====== DUSP2 (PAC1) ====== | ||
| + | DUSP2 prefers to dephosphorylate ERK and p38 over JNK. As shown in crystal structure, similar with other MKPs, the rhodanese domain and phosphatase domain are directly coupled to MAPK-induced conformational change of the phosphatase active site, which is essential for eliciting its full enzymatic activity <cite>Farooq03</cite>. | ||
| + | |||
| + | === References === | ||
| + | <biblio> | ||
| + | #Farooq03 pmid=12575935 | ||
| + | #Patterson09 pmid=19228121 | ||
| + | </biblio> | ||
Revision as of 01:41, 6 March 2015
Phosphatase Classification: Superfamily CC1: Family DSP: Subfamily DSP1
summary....
Evolution
DSP1 subfamily is widely found across eukaryotes. It is present in animals, plants, amoeba, and some basal eukaryotes, but is absent from ecdysozoa (nematodes and arthropods), most fungi and monosiga (unpublished data, DUSP1, DUSP2, DUSP4, DUSP5).
Domain Structure
DSP1 has an inactive Rhodanese domain, followed by a CC1-fold phosphatase domain.
Functions
In general, DSP1 are inducible nuclear MAP Kinase phosphatases (MKPs), also known as the Group A DSPs. Human members are DUSP1, DUSP2, DUSP4 and DUSP5. Their substrate specificity, subcellular localization and etc have been summarized in Table 1 in review paper [1].
DUSP1 (MKP1/hVH1)
DUSP1 is the best characterized phosphatase within this subfamily. It prefers to dephosphorylates p38 and JNK over ERK. DUSP1 is involved in immune regulation and cancer. DUSP1 is an important negative-feedback regulator of macrophage function and the inflammatory response to TLR signalling, and plays key regulatory roles in both innate and adaptive immune responses via inactivation of p38 and JNK (reviewed in [1]). It is worthy pointing out that DUSP1 expression is strictly regulated in brain (see GTEx).
(PS: more reading is needed).
DUSP2 (PAC1)
DUSP2 prefers to dephosphorylate ERK and p38 over JNK. As shown in crystal structure, similar with other MKPs, the rhodanese domain and phosphatase domain are directly coupled to MAPK-induced conformational change of the phosphatase active site, which is essential for eliciting its full enzymatic activity [2].
References
- Patterson KI, Brummer T, O'Brien PM, and Daly RJ. Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J. 2009 Mar 15;418(3):475-89. DOI:10.1042/bj20082234 |
- Farooq A, Plotnikova O, Chaturvedi G, Yan S, Zeng L, Zhang Q, and Zhou MM. Solution structure of the MAPK phosphatase PAC-1 catalytic domain. Insights into substrate-induced enzymatic activation of MKP. Structure. 2003 Feb;11(2):155-64. DOI:10.1016/s0969-2126(02)00943-7 |
