Difference between revisions of "Phosphatase Subfamily STS"
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=== Domain === | === 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 | + | 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 === | === Functions === | ||
Revision as of 16:55, 15 May 2016
Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: 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.
Evolution
STS subfamily is found in most 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.
Domain
Most STS have four domains: UBA (ubiquitin-associated domain), 2H phosphoesterase [1], SH3 and HP2 phosphatase domain. The UBA, 2H and SH3 domains are absent from all nematode members (see technical notes).
Functions
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 GTEx), whereas STS-1/TULA2/UBASH3B is expressed ubiquitously (according to GTEx, particularly abundant in cerebellum (not whole brain)).
STS-1 decreases tyrosine phosphorylation of Syk in vivo and in vitro [2, 3]. 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 [4]. In addition, both STS-1 and STS-2 regulates kinase ZAP-70 activation [3].
Human STS-1 can also dephosphorylate phospho-tyrosines on EGFR [5] and is overexpressed in triple-negative breast cancer and promotes invasion and metastasis [6]. 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 [5].
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.
References
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