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Dual-specificity phosphatase
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<h2 id="classification">Classification</h2> <p>The human genome encodes at least 61 different DUSP proteins. The following major groups or families of DUSPs were identified:<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <ul><li>Slingshot phosphatases:</li></ul> <p>There are three members of this family (<a href="/facts/SSH1/LwPrusyo">SSH1</a>L, <a href="/facts/SSH2/lU427oke">SSH2</a>L and <a href="/facts/SSH3/vUTyN80c">SSH3</a>L) with broad specificity. They contain SH3-binding motifs as well as F-actin binding motifs, thus they are generally believed to play a role in the regulation of cytoskeletal rearrangements. In accordance with their proposed rule, proteins like ADF, cofilin and LIMK1 are slingshot substrates. </p> <ul><li>Phosphatases of Regenerating Liver (PRLs):</li></ul> <p>Three PRL genes were described in mammals (PRL-1, PRL-2 and PRL-3). They share a high sequence identity and possess an N-terminal prenylation sequence (CAAX box). Despite their up-regulation in colorectal cancer, the role and substrate specificity of PRLs is poorly known. </p> <ul><li><a href="/facts/Cdc14/8q6aTfko">Cdc14</a> phosphatases:</li></ul> <p>The four mammalian Cdc14 proteins (named KAP, Cdc14A, Cdc14B and PTP9Q22) play a crucial role in cell cycle regulation by dephosphorylating cyclin-dependent kinases, most importantly CDK2. </p> <ul><li><a href="/facts/PTEN_(gene)/Xg6MAcHm">PTEN</a> and <a href="/facts/Myotubularin/0YIy4Tw1">myotubularin</a> phosphatases</li></ul> <p>There are five PTEN-like phosphatases encoded in the human genome. Though structurally related to other DUSPs, these are not strictly phosphorotein-phosphatases, since their most important substrates are phosphorylated inositol lipids. Myotubularins similarly display a preference towards certain phosphatidyl inositols. </p> <ul><li><a href="/facts/MAPK_phosphatase/EeN4eKtn">Mitogen-activated protein Kinase Phosphatases</a> (MKPs)</li></ul> <p>MKPs form a rather large family, with some 11 well-characterized members. They are responsible for the dephosphorylation of active mitogen-activated protein kinases (MAPKs). In accordance with this role, several (but not all) MKPs contain an additional, N-terminal domain. Although structurally similar to Cdc14, this extra domain is inactive, and plays a role in substrate recruitment. The surface of this substrate-binding domain mimics the D-motifs found in intrinsically disordered substrates of MAPKs. </p> <ul><li>In addition, there are several dual-specificity phosphatases lacking close relatives. Most of these atypical DUSPs are poorly characterized. Some of them are probably inactive, and only mediate protein-protein interactions.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Dual-Specificity+Phosphatases at the U.S. National Library of Medicine Medical Subject Headings (MeSH) <a href="https://meshb.nlm.nih.gov/record/ui?name=Dual-Specificity+Phosphatases" target="_blank">https://meshb.nlm.nih.gov/record/ui?name=Dual-Specificity+Phosphatases</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Denu JM, Dixon JE (June 1995). "A catalytic mechanism for the dual-specific phosphatases". Proc. Natl. Acad. Sci. U.S.A. 92 (13): 5910–4. doi:10.1073/pnas.92.13.5910. PMC 41611. PMID 7597052. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41611" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41611</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Patterson KI, Brummer T, O'Brien PM, Daly RJ (March 2009). "Dual-specificity phosphatases: critical regulators with diverse cellular targets". Biochem. J. 418 (3): 475–89. doi:10.1042/bj20082234. PMID 19228121. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Patterson KI, Brummer T, O'Brien PM, Daly RJ (March 2009). "Dual-specificity phosphatases: critical regulators with diverse cellular targets". Biochem. J. 418 (3): 475–89. doi:10.1042/bj20082234. PMID 19228121. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> </ol>