Phosphatase Subfamily STS - Revision history

Gerard at 20:53, 10 July 2017

2017-07-10T20:53:49Z

Gerard at 21:48, 25 October 2016

2016-10-25T21:48:31Z

Mark: /* References */

2016-08-31T20:06:14Z

‎References

Gerard: /* Evolution */

2016-05-15T17:44:27Z

‎Evolution

Gerard at 17:41, 15 May 2016

2016-05-15T17:41:22Z

Gerard at 17:41, 15 May 2016

2016-05-15T17:41:06Z

Gerard: /* Functions */

2016-05-15T17:35:05Z

‎Functions

Gerard at 17:25, 15 May 2016

2016-05-15T17:25:43Z

Gerard at 16:56, 15 May 2016

2016-05-15T16:56:10Z

Gerard: /* Domain */

2016-05-15T16:55:38Z

‎Domain

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 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]]:  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_STS|Subfamily STS]]
-STS is protein tyrosine phosphatase involved in T-cell receptor signaling. In particular, STS dephosphorylates kinases Syk and ZAP-70 of Syk subfamily. STS is conserved in metazoan.
+STS is protein tyrosine phosphatase involved in T-cell receptor signaling by dephosphorylating the Syk and ZAP-70 kinases. STS is found throughout metazoa.
 === Evolution ===

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 __NOTOC__
-[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_STS|Subfamily STS]]
+[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]]:  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_STS|Subfamily STS]]
 STS is protein tyrosine phosphatase involved in T-cell receptor signaling. In particular, STS dephosphorylates kinases Syk and ZAP-70 of Syk subfamily. STS is conserved in metazoan.

@@ Line 34: / Line 34: @@
 #Sullivan pmid=19060182
 #Yamada pmid=12721294
-#Zhang pmid 26365512
+#Zhang pmid=26365512
 </biblio>

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 === Evolution ===
-STS is found in most [[Phosphatase_Glossary#metazoa|metazoa]]. Human has two STSs: STS1 (TULA-2 or UBASH3B) and STS2 (TULA-1 or UBASH3A). STS2 is present in lobe-finned fish, birds and mammals, but not other bony fishes. STS1 emerged earlier than STS2, which is found in most metazoa, from sponge to insects, fishes, birds, and mammals. ''C. elegans'' has five STS genes, but all of them lack UBA (ubiquitin-associated domain), 2H phosphoesterase, and SH3 domains. Interestingly, STS substrates, Syk and ZAP-70, both of which belong to SYK kinase family, are absent from ''C. elegans''.
+STS is found in most [[Phosphatase_Glossary#metazoa|metazoa]]. Human has two STS: STS1 (TULA-2 or UBASH3B) and STS2 (TULA-1 or UBASH3A). STS1 is found in all vertebrates, while STS2 is not found in bony fish. ''C. elegans'' has five STS genes, but all of them lack UBA (ubiquitin-associated domain), 2H phosphoesterase, and SH3 domains. Interestingly, STS substrates, Syk and ZAP-70, both of which belong to SYK kinase family, are absent from ''C. elegans''.
 === Domain ===

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 === Evolution ===
-STS subfamily is found in most [[Phosphatase_Glossary#metazoa|metazoa]]. Human has two STSs: STS1 (TULA-2 or UBASH3B) and STS2 (TULA-1 or UBASH3A). STS2 is present in lobe-finned fish, birds and mammals, but not other bony fishes. STS1 emerged earlier than STS2, which is found in most metazoa, from sponge to insects, fishes, birds, and mammals. ''C. elegans'' has five STS genes, but all of them lack UBA (ubiquitin-associated domain), 2H phosphoesterase, and SH3 domains. Interestingly, STS substrates, Syk and ZAP-70, both of which belong to SYK kinase family, are absent from ''C. elegans''.
+STS is found in most [[Phosphatase_Glossary#metazoa|metazoa]]. Human has two STSs: STS1 (TULA-2 or UBASH3B) and STS2 (TULA-1 or UBASH3A). STS2 is present in lobe-finned fish, birds and mammals, but not other bony fishes. STS1 emerged earlier than STS2, which is found in most metazoa, from sponge to insects, fishes, birds, and mammals. ''C. elegans'' has five STS genes, but all of them lack UBA (ubiquitin-associated domain), 2H phosphoesterase, and SH3 domains. Interestingly, STS substrates, Syk and ZAP-70, both of which belong to SYK kinase family, are absent from ''C. elegans''.
 === Domain ===

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 === Evolution ===
-STS subfamily is found in most [[Phosphatase_Glossary#metazoa|metazoa]]. Human has two STSs: STS-1 (TULA-2 or UBASH3B) and STS-2 (TULA-1 or UBASH3A). STS-2 is present in lobe-finned fish, birds and mammals, but not other bony fishes. STS-1 emerged earlier than STS-2, which is found in most metazoan, from sponge to insects, fishes, birds, and mammals. ''C. elegans'' has five STS genes, but all of them lack UBA (ubiquitin-associated domain), 2H phosphoesterase, and SH3 domains. Interestingly, STS substrates, Syk and ZAP-70, both of which belong to SYK kinase family, is absent from ''C. elegans''.
+STS subfamily is found in most [[Phosphatase_Glossary#metazoa|metazoa]]. Human has two STSs: STS1 (TULA-2 or UBASH3B) and STS2 (TULA-1 or UBASH3A). STS2 is present in lobe-finned fish, birds and mammals, but not other bony fishes. STS1 emerged earlier than STS2, which is found in most metazoa, from sponge to insects, fishes, birds, and mammals. ''C. elegans'' has five STS genes, but all of them lack UBA (ubiquitin-associated domain), 2H phosphoesterase, and SH3 domains. Interestingly, STS substrates, Syk and ZAP-70, both of which belong to SYK kinase family, are absent from ''C. elegans''.
 === Domain ===
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 === Functions ===
-Human STS1 and STS2 bind to the Cbl protein via their SH3 domains and interact with several membrane-associated signaling proteins. In particular, STS regulates T Cell Receptor (TCR) signaling by acting on the [http://kinase.com/wiki/index.php/Kinase_Family_Syk Syk family] kinases, Syk and ZAP-70. STS-2/TULA1/UBASH3A is predominantly in naive and mature T cells (white blood, spleen and small intestine, according to [http://www.gtexportal.org/home/gene/UBASH3A GTEx]), whereas STS-1/TULA2/UBASH3B is expressed ubiquitously (according to [http://www.gtexportal.org/home/gene/UBASH3B GTEx], particularly abundant in cerebellum (not whole brain)).
+Human STS1 and STS2 bind to the Cbl protein via their SH3 domains and interact with several membrane-associated signaling proteins  <cite>STS_2</cite>. In particular, STS regulates T Cell Receptor (TCR) signaling by acting on the [http://kinase.com/wiki/index.php/Kinase_Family_Syk Syk family] kinases, Syk and ZAP-70. STS2 is predominantly in naive and mature T cells (white blood, spleen and small intestine, according to [http://www.gtexportal.org/home/gene/UBASH3A GTEx]), whereas STS1 is expressed ubiquitously (according to [http://www.gtexportal.org/home/gene/UBASH3B GTEx], particularly abundant in cerebellum).
-STS-1 decreases tyrosine phosphorylation of Syk ''in vivo'' and ''in vitro'' <cite>chen10, carpino04</cite>. Inactivated STS-1 increases tyrosine phosphorylation of Syk in cells co-transfected to overexpress these proteins, thus acting as a dominant-negative form that suppresses dephosphorylation of Syk caused by endogenous STS-1. However, the same assay on STS-2 shows the phosphatase activity of STS-2 is negligible compared to STS-1. The UBA domain of STS-2 and SH3-dependent Cbl-binding are required for this function <cite>STS_2</cite>. In addition, both STS-1 and STS-2 regulate kinase ZAP-70 activation <cite>carpino04</cite>.
+STS1 decreases tyrosine phosphorylation of Syk ''in vivo'' and ''in vitro'' <cite>chen10, carpino04</cite>, and this is reversed by transfection of an inactive STS1 mutant. In addition, both STS1 and STS2 regulate kinase ZAP-70 activation <cite>carpino04</cite>.
-Human STS-1 can also dephosphorylate pTyr on EGFR <cite>STS_1</cite> and is overexpressed in triple-negative breast cancer and promotes invasion and metastasis <cite>Lee13</cite>. STS-1 dephosphorylated the EGFR at multiple tyrosines, terminating its signalling and endocytosis <cite>STS_1</cite>. STS1 and STS2 also dephosphorylate the receptor tyrosine kinases Kit and Flt3, and double knockout mice show greatly expanded hematopoiesis <cite>Zhang</cite>.
+Human STS1 can also dephosphorylate pTyr on EGFR <cite>STS_1</cite> and is overexpressed in triple-negative breast cancer and promotes invasion and metastasis <cite>Lee13</cite>. STS1 dephosphorylated the EGFR at multiple tyrosines, terminating its signalling and endocytosis <cite>STS_1</cite>. STS1 and STS2 also dephosphorylate the receptor tyrosine kinases Kit and Flt3, and double knockout mice show greatly expanded hematopoiesis <cite>Zhang</cite>.
 Drosophila STS (CG13604) was shown to have activity on phosphorylated ecdysteroids, the storage form of these molting hormones, and the C. elegans homolog T07F12.1 also had activity <cite><Davies</cite>. A silkworm homolog was also shown to have ecdysteroid phosphatase activity <cite>Yamada</cite>. An Unclassified HP1-family yeast phosphatase, [http://phosphatome.net/3.0/database/gene/uid/ScerP017 DET1] has been implicated in sterol trafficking <cite>Sullivan</cite>, but it is not known if phosphatase activity is involved.
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 === Technical notes ===
 ===== Nematodes lost UBA, 2H and SH3 domain =====
-We observed the absence of UBA, 2H and SH3 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 STSs from our internal orthology database, which has 203 eukaryotic genomes and 9 nematode genomes. We then searched Pfam domain in the STSs using Pfam web server (E-value cutoff 1.0). We found none of the 24 DSPs from 9 nematode genomes has UBA, 2H or SH3 domain.
+Loss of UBA, 2H and SH3 domain was seen in all C. elegans STS. NCBI Blast, interrogation of an internal orthology database, and Pfam profiling were used to show that all other nematode STS proteins also lack these domains.
 ===References===

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 Human STS-1 and STS-2 are involved in T Cell Receptor (TCR) signaling pathways by regulating kinase Syk and ZAP-70, two members of Syk kinase subfamily. STS-2/TULA1/UBASH3A is predominantly in naive and mature T cells (white blood, spleen and small intestine, according to [http://www.gtexportal.org/home/gene/UBASH3A GTEx]), whereas STS-1/TULA2/UBASH3B is expressed ubiquitously (according to [http://www.gtexportal.org/home/gene/UBASH3B GTEx], particularly abundant in cerebellum (not whole brain)).
-STS-1 decreases tyrosine phosphorylation of Syk ''in vivo'' and ''in vitro'' <cite>chen10, carpino04</cite>. Inactivated STS-1 increases tyrosine phosphorylation of Syk in cells co-transfected to overexpress these proteins, thus acting as a dominant-negative form that suppresses dephosphorylation of Syk caused by endogenous STS-1. However, the same assay on STS-2 shows the phosphatase activity of STS-2 is negligible compared to STS-1. The UBA domain of STS-2 and SH3-dependent Cbl-binding are required for this function <cite>STS_2</cite>. In addition, both STS-1 and STS-2 regulates kinase ZAP-70 activation <cite>carpino04</cite>.
+STS-1 decreases tyrosine phosphorylation of Syk ''in vivo'' and ''in vitro'' <cite>chen10, carpino04</cite>. Inactivated STS-1 increases tyrosine phosphorylation of Syk in cells co-transfected to overexpress these proteins, thus acting as a dominant-negative form that suppresses dephosphorylation of Syk caused by endogenous STS-1. However, the same assay on STS-2 shows the phosphatase activity of STS-2 is negligible compared to STS-1. The UBA domain of STS-2 and SH3-dependent Cbl-binding are required for this function <cite>STS_2</cite>. In addition, both STS-1 and STS-2 regulate kinase ZAP-70 activation <cite>carpino04</cite>.
-Human STS-1 can also dephosphorylate phospho-tyrosines on EGFR <cite>STS_1</cite> and is overexpressed in triple-negative breast cancer and promotes invasion and metastasis <cite>Lee13</cite>. The histidine phosphatase domain of STS-1, but not of STS-2, dephosphorylates the EGFR at multiple tyrosines, and thereby terminating its signalling and endocytosis <cite>STS_1</cite>.
+Human STS-1 can also dephosphorylate pTyr on EGFR <cite>STS_1</cite> and is overexpressed in triple-negative breast cancer and promotes invasion and metastasis <cite>Lee13</cite>. STS-1 dephosphorylated the EGFR at multiple tyrosines, terminating its signalling and endocytosis <cite>STS_1</cite>. STS1 and STS2 also dephosphorylate the receptor tyrosine kinases Kit and Flt3, and double knockout mice show greatly expanded hematopoiesis <cite>Zhang</cite>.
 === Technical notes ===
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 ===References===
 <biblio>
 #STS_1 pmid=17880946
 #STS_2 pmid=18189269
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 #Lee13 pmid=23784775
 #mazumder02 pmid=12466548
 </biblio>

← Older revision		Revision as of 16:56, 15 May 2016
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		+	__NOTOC__
	[[Phosphatase classification\|Phosphatase Classification]]: [[Phosphatase_Fold_HP\|Fold HP]]: [[Phosphatase_Superfamily_HP\|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP1\|HP, branch1 family]]: [[Phosphatase_Subfamily_STS\|Subfamily STS]]		[[Phosphatase classification\|Phosphatase Classification]]: [[Phosphatase_Fold_HP\|Fold HP]]: [[Phosphatase_Superfamily_HP\|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP1\|HP, branch1 family]]: [[Phosphatase_Subfamily_STS\|Subfamily STS]]

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 === Domain ===
-Most STS have four domains: [[Phosphatase_Glossary#Domain_UBA|UBA]]  (ubiquitin-associated domain), 2H phosphoesterase <cite>mazumder02</cite>, [[Phosphatase_Glossary#Domain_SH3|SH3]] and HP2 phosphatase domain. The UBA, 2H and SH3 domains are absent from ''C. elegans'' STSs and from nematodes in general (see technical notes).
+Most STS have four domains: [[Phosphatase_Glossary#Domain_UBA|UBA]]  (ubiquitin-associated domain), 2H phosphoesterase <cite>mazumder02</cite>, [[Phosphatase_Glossary#Domain_SH3|SH3]] and HP2 phosphatase domain. The UBA, 2H and SH3 domains are absent from all nematode members (see technical notes).
 === Functions ===