Phosphatase Subfamily DSP6 - Revision history

Gerard at 19:02, 20 February 2018

2018-02-20T19:02:48Z

Gerard at 19:02, 20 February 2018

2018-02-20T19:02:36Z

Mark: /* Domain */

2016-02-05T18:11:46Z

‎Domain

Mark: /* Nematodes lost rhodanese domain */

2016-02-05T18:11:31Z

‎Nematodes lost rhodanese domain

Mark: /* References */

2015-09-22T17:19:23Z

‎References

Mark: /* DUSP6 (MKP3/PYST1) */

2015-09-22T17:18:58Z

‎DUSP6 (MKP3/PYST1)

Mark: /* Nematodes lost rhodanese domain */

2015-06-29T19:42:06Z

‎Nematodes lost rhodanese domain

Mark: /* Nematodes lost rhodanese domain */

2015-06-29T18:46:35Z

‎Nematodes lost rhodanese domain

Mark at 18:37, 29 June 2015

2015-06-29T18:37:57Z

Mark: /* Domain */

2015-06-29T18:33:04Z

‎Domain

← Older revision		Revision as of 19:02, 20 February 2018
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		+	__NOTOC__
	[[Phosphatase classification\|Phosphatase Classification]]: [[Phosphatase_Fold_CC1\|Fold CC1]]: [[Phosphatase_Superfamily_CC1\|Superfamily CC1]]: [[Phosphatase_Family_DSP\|Family DSP]]: [[Phosphatase_Subfamily_DSP6\|Subfamily DSP6]]		[[Phosphatase classification\|Phosphatase Classification]]: [[Phosphatase_Fold_CC1\|Fold CC1]]: [[Phosphatase_Superfamily_CC1\|Superfamily CC1]]: [[Phosphatase_Family_DSP\|Family DSP]]: [[Phosphatase_Subfamily_DSP6\|Subfamily DSP6]]

@@ Line 1: / Line 1: @@
 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]:  [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_DSP6|Subfamily DSP6]]
-DSP6 is a cytoplasmic MKP subfamily selectively dephoshorylating ERK. It is found throughout metazoan and duplicated in vertebrates.  Human genome has three members: DUSP6 (MKP3), DUSP7 (MKPX) and DUSP9 (MKP4).
+DSP6 is a metazoan cytoplasmic MKP subfamily that selectively dephosphorylates ERK.
 === Evolution ===
-DSP6 is found throughout metazoan. It duplicated in vertebrates. There are three members in human, DUSP6, DUSP7 and DUSP9.
+DSP6 is found throughout metazoa. It duplicated in vertebrates. The three human members are DUSP6 (MKP3), DUSP7 (MKPX) and DUSP9 (MKP4).
 === Domain ===
-DSP6 subfamily has two domains: rhodanese domain and phosphatase domain.
+DSP6 has two domains: rhodanese domain and phosphatase domain.
-Rhodanese domain inhibit phosphatase domain activity in DUSP6 <cite>Camps98</cite>, which is achieved by the binding of rhodanese domain and phosphatase domain. The binding stabilizes the inactive conformation of the phosphatase catalytic site <cite>Mark08</cite>. The rhodanese domain also mediates interaction with MAP kinases (often ERK) ('''via kinase interaction motif?'''). Its binding to MAP kinases induces conformation change in phosphatase domain, which can increase the phosphatase activity <cite>Stewart99</cite>.
+The rhodanese domain inhibit phosphatase domain activity in DUSP6 <cite>Camps98</cite>, which is achieved by the binding of rhodanese domain and phosphatase domain. The binding stabilizes the inactive conformation of the phosphatase catalytic site <cite>Mark08</cite>. The rhodanese domain also mediates interaction with MAP kinases (often ERK) ('''via kinase interaction motif?'''). Its binding to MAP kinases induces conformation change in phosphatase domain, which can increase the phosphatase activity <cite>Stewart99</cite>.
 Rhodanese domain of DSP6 also has two conserved Leu-rich nuclear export signals <cite>Karlsson04</cite> (particular Figure 5 and Figure 11).
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 ====== DUSP6 (MKP3/PYST1) ======
-DUSP6 preferentially dephosphorylates ERK <cite>Muda96, Groom96, Kim03</cite>, which resulted from that DUSP6 binds to ERK but not p38 or JNK. The interaction is mediated by rhodanese domain (or kinase interaction motif embedded in rhodanese domain?) <cite>Muda98</cite>. Later study has shown DUSP6 is ERK1/2-specific, as it does not inactive ERK5 <cite>Arkell08</cite>.
+DUSP6 preferentially dephosphorylates ERK <cite>Muda96, Groom96, Kim03</cite>, due to ability of DUSP6 to bind ERK but not p38 or JNK. The interaction is mediated by rhodanese domain (or kinase interaction motif embedded in rhodanese domain?) <cite>Muda98</cite>. Later study has shown DUSP6 is ERK1/2-specific, as it does not inactive ERK5 <cite>Arkell08</cite>.
 Furthermore, DUSP6, ERK2, and phosphorylated p38alpha can form a stable ternary complex in solution, and the phosphatase activity of DUSP6 toward p38alpha substrate is allosterically regulated by ERK2-DUSP6 interaction. This suggests that DUSP6 may mediate cross-talk between ERK and p38 pathways <cite>Zhang11</cite>. ('''note: this is perhaps the mechanism behind DUSP6 modules DNA damage response <cite>Bagnyukova13</cite>.''')
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 === Technical notes ===
 ===== Nematodes lost rhodanese domain =====
-We observed the absence of rhodanese domain in C. elegans. We then asked whether the lose is conserved, which can be use to measure the reliability of the lose. We obtained DSP6s from our internal orthology database, which has 203 eukaryotic genomes and 9 nematode genomes. We then searched Pfam domain in the DSP6s using Pfam web server (E-value cutoff 1.0). We found none of the 10 nematode DSPs from 7 nematode genomes has rhodanese domain. The DSP6 subfamily is not found in another 2 nematode genomes: Pristionchus pacificus and Loa loa.
+We observed the absence of rhodanese domain in C. elegans. We then asked whether the loss is conserved, which can be use to measure the reliability of the loss. We obtained DSP6s from our internal orthology database, which has 203 eukaryotic genomes and 9 nematode genomes. We then searched Pfam domain in the DSP6s using Pfam web server (E-value cutoff 1.0). We found none of the 10 nematode DSPs from 7 nematode genomes has rhodanese domain. The DSP6 subfamily is not found in another 2 nematode genomes: Pristionchus pacificus and Loa loa.
 We also BLASTed human DUSP6 against nematode NR protein data set. We found rhodanese-containing DSP6 in most Trichocephalida, which suggest the lost in happened posterior to  Trichocephalida diverged from other nematodes.

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 Rhodanese domain of DSP6 also has two conserved Leu-rich nuclear export signals <cite>Karlsson04</cite> (particular Figure 5 and Figure 11).
-The rhodanese domain was lost in nematodes (see technical notes).
+The rhodanese domain was lost in many nematodes (see technical notes).
 === Function ===

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 ===== Nematodes lost rhodanese domain =====
 We observed the absence of rhodanese domain in C. elegans. We then asked whether the lose is conserved, which can be use to measure the reliability of the lose. We obtained DSP6s from our internal orthology database, which has 203 eukaryotic genomes and 9 nematode genomes. We then searched Pfam domain in the DSP6s using Pfam web server (E-value cutoff 1.0). We found none of the 10 nematode DSPs from 7 nematode genomes has rhodanese domain. The DSP6 subfamily is not found in another 2 nematode genomes: Pristionchus pacificus and Loa loa.
 === References ===

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 #Karlsson04 pmid=15269220
 #Kim03 pmid=14690430
 #Lee11 pmid=21680106
 #Lee12 pmid=22535643

← Older revision		Revision as of 17:18, 22 September 2015
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	('''note: DUSP6 upregulation in cancer could be explained by feedback mechanisms?''')		('''note: DUSP6 upregulation in cancer could be explained by feedback mechanisms?''')
		+
		+	DUSP6 (MKP3) inhibits brown adipocyte differentiation perhaps via regulation of Erk phosphorylation <cite>Kim15</cite>.

	Like DUSP2, DUSP4 and DUSP4 of DSP1 subfamily, DUSP6 is phosphorylated by ERK <cite>Marchetti05</cite>. However, the phosphorylation sites are different. DUSP6 is phosphorylated at serines 159 and 197 <cite>Marchetti05</cite>, which are found in DUSP6 and DUSP7, but not DUSP9 or other DSPs.		Like DUSP2, DUSP4 and DUSP4 of DSP1 subfamily, DUSP6 is phosphorylated by ERK <cite>Marchetti05</cite>. However, the phosphorylation sites are different. DUSP6 is phosphorylated at serines 159 and 197 <cite>Marchetti05</cite>, which are found in DUSP6 and DUSP7, but not DUSP9 or other DSPs.