Difference between revisions of "Phosphatase Subfamily PTPRA"

Revision as of 19:10, 19 February 2015

Phosphatase Classification: Superfamily CC1: Family PTP: Subfamily PTPRA

PTPRA is a deuterostome-specific receptor PTP subfamily

Evolution

PTPRA and PTPRE are related human genes with homologs across vertebrates. No conclusive invertebrate homologs have been found, though the phosphatase domains are most similar to the invertebrate Ptp69D subfamily. Phosphatase fragments in Branchiostoma, Ciona and Urchin are most similar to vertebrate PTPRA and may well be orthologous. The Ciona gene has a long array of Sushi, mucin and ricin domains on the extracellular region, and the other two are fragments lacking the putative extracellular region. See PTPRA-details.

Domain Structure

All members have twin intracellular PTP phosphatase catalytic domains and a conserved juxtamembrane region of ~90 AA between the transmembrane region and the first PTP domain. Both have short, poorly conserved extracellular regions and neither are known to bind ligand. In human PTPRA, the extracellular region is 132 AA long, has poor conservation even between mammals and fish and low sequence complexity. NCBI CDD annotates it weakly as an endomucin domain, a region found in several surface-expressed endothelial proteins (Pfam: PF07010 [1]). No sequence similarity is seen to any protein other than vertebrate PTPRA. PTPRE has multiple splice forms, including one with an alternative N-terminus that lacks a signal peptide, and one with a 26 AA extracellular region, which is also poorly conserved between vertebrate homologs. The intracellular juxtamembrane region (upstream of the PTP domains) of ~88 AA is highly conserved between vertebrate homologs.

An additional splice form of PTPRE has been reported, which replaces the second PTP domain with a unique tail [1].

Functions

Human PTPRA and PTPRE are candidate phosphatases of Src kinases [2, 3].

In mouse, overexpression of PTPRE resulted in lower levels of IL-6-induced tyrosine phosphorylation of Jak1, Tyk2, gp130, and Stat3, which suggested that PTPRE is involved in negative regulation of IL-6- and LIF-induced Jak-STAT signaling [4].

References

1. Error fetching PMID 12193229: [Wabakken]
2. Error fetching PMID 17212655: [kapp07]
3. Error fetching PMID 15845350: [roskoski05]
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