Fig 1.
Domain architecture of human R3 RPTP members.
Schematic representation of human R3 subtype RPTP protein members. For catalytic PTP, FN3 and signal peptide symbols see the figure. Black and light blue boxes represent the transmembrane segments and the cytoplasmatic regions after the PTP domain, respectively. Note the larger size of the juxtamembrane FN3 domain in PTPRQ, PTPRB and PTPRJ proteins [15]. Protein amino acid numbers are indicated in parenthesis below the protein names.
Fig 2.
Invertebrate and vertebrate PTP domain similarity.
Heat map representing color-coded blastp E value of PTP domains of R3 PTPRs from vertebrates and inverebrates deuterostomes, protostomes and sponges. Note the strong similarity of the sponge PTP sequence with PTPRF and PTPRG. E values are coloured from green (low similarity) to red (high similarity) (See S1 Table for numerical E values; 100% similarity corresponds to an E value of 0.0). Full scientific names of species are: Co, Capsaspora owczarzaki; Aq, Amphimedon queenslandica; Ct, Capitella teleta; Dm, Drosophila melanogaster; Ce, Caenorhabditis elegans; Hc, Haemonchus contortus; Sp, Strongylocentrotus purpuratus; Sk, Saccoglossus kowalevskii; Cs, Ciona Savigny; Ci, Ciona intestinalis; Hs, Homo sapiens. Other sequences Chicken (Gg) Gallus gallus; Fish (Dr) Danio rerio.
Fig 3.
Protein and DNA trees showing the evolutionary relationships between RPTPs.
A) Bayes protein concatenated tree (see text for description of model parameters and analysis specifics). Values at the nodes in the tree indicate the Bayesian posterior probability for that node. B) DNA elide Bayes tree (see text for description of model parameters and analysis specifics). Values at the nodes in the tree indicate the Bayesian posterior probability for that node. Protein and DNA parsimony, and additional Bayesian phylogenetic trees are included in S2 File.
Fig 4.
Structural characteristics and evolution of vertebrate and invertebrate R3 RPTPs.
A) Protein tree from Fig 3 with metazoan sequences. The vertebrate clusters of R3 RPTPs are indicated by vertical lines of different colours. B) Carboxy terminus predicted tyrosine phosphorylation sites. Blue bold Y and N letters represent, respectively, the tyrosine predicted phosphorylation residue and the asparagine residue of the YxN motif of RPTP phosphorylation sites in some mammalian proteins [14]. Small x in PTPRB prediction sites represents any amino acid. Dashed horizontal lines indicate negative phosphorylation prediction. C) Aspartic acid modifications in the WPD loop of the catalytic domain. Divergent amino acids from the canonical WPD motif residues are indicated in red bold letters. The replacement of WPD with WPE in PTPRQs changes their substrate specificity from phospho tyrosine to inositol phosphate [11]. D) FN3 B-C loops. The distances between the loop flanking tryptophan (W) and tyrosine (Y) residues and the distance to a conserved glycine residue inside the loop were coded with different colors and plotted in the tree. Codes are of the form WnGnY where n indicates the number of amino acid residues between the W-G or G-Y residues. The alignments of the FN3 domains are provided in S2 Fig. Colour codes are: red, W4G4Y; orange W4G5Y; light blue W4G7Y; green W5G4Y; yellow W7G3Y; dark blue W7G4Y; lavender W9G2Y; and pink W9G4Y. White colour represents different codes from the above codes. E) FN3 intron/exon structure. FN3 domains flanked by two introns in phase 1 (1:1) are represented as yellow squares; with an additional intron inside the domain in phase 0 as orange squares (1:0:1), in phase 1 as blue squares (1:1:1) or in phase 2 as black squares (1:2:1). The larger juxtamembrane FN3 domains (1:1:2:1:2) are represented by grey squares. White squares indicate FN3 domains with intron codes different from the above. Absence of FN3 flanking introns is indicated by absence of the vertical sides of the squares.
Fig 5.
Synteny relationship between vertebrate PTPRBs and C. intetinalis Ciona_1 locus.
Genes shown are those close to the PTPRB locus in human, the early diverged vertebrate spotted gar and around Ciona_1 locus (ENSCING00000003151) in the sea squirt (C. intestinalis). Blue lines indicate conserved genes and black lines indicate genes not present in the ciona genome. The genomic localization of the different genes is indicated below the gene name. The chromosome or scaffold number in the ciona genome for the genes present around PTPRB in vertebrates but not around the Ciona_1 gene in Chr.2 are also indicated. ENSEMBL Ciona genes are: CCT2 ENSCING00000005347; BEST3: ENSCING00000006827; CNOT2:ENSCING00000006804 or ENSCING00000021615; PTPRR ENSCING00000000420; LGR5 ENSCING00000018199 (see also S4 Fig).