The domain interface. The second phenylalanine side chain sticks into the
The domain interface. The second phenylalanine side chain sticks in to the core of C2, and histidine side chain is in the interface. A third conserved motif, KX(DE)L(DE)X5(RK) [Fig. (E)], is distinguished by numerous ionizable side chains. It adopts helical structure in the domain interface in PTEN, forming contacts using the Nterminus of theHaynie and XuePROTEIN SCIENCE VOL 24:874either no domain is positioned downstream of PTPC2, as in PTEN, or PTPC2 is followed by J, SH2 or PTB, as in GAK and tensins.2 PTPC2 inside the aquatic organisms (triangles) is significantly less simple than Stattic web within the terrestrial animals. The arrow indicates a attainable exception. PTENlike, this Helobdella robusta protein consists of just PTPC2. The pI of human PTEN is eight.05 (star). Two, evaluation from the signature motif [Fig. (A)] suggests the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24638984 value of an acidic side chain in the active website. In human TNS3, for instance, the sequence is WPE. . .IHCRGGKGRI. The Glu side chain, although distant in sequence in the Cys nucleophile, may well function as a general acid in the phosphatase reaction mechanism.30 This residue is Asp in human PTEN. In about 2 of your present proteins, by contrast, the corresponding side chain can’t ionize. In the Capitella teleta protein this residue is Gln, and within the Riptortus pedestris protein it is actually Pro. Ten of 2 such instances are correlated with all the insubstitution of an acidic side chain within the signature motif. In the C. teleta protein the motif is WPQ. . .IHSKGERGRS. The Capsaspora owczarzaki and Paramecium tetraurelia proteins are exceptions.Figure two. Place in PTEN of your PTPC2 superdomain conserved motifs. The PTP domain is at the top rated in each and every case, the C2 domain in the bottom. A) Motif , PS(QH)(K R)RYUXYF. B) Motif 2, U2GDU3(RK)UYH. C) Motif three, UFXUQFHTU2. D) Motif four, KX(DE)L(DE)X5(RK). All atoms of every single residue in every single motif are shown spacefilled and colored orange. The D5R structure was utilized for visualization.PTPC2 evolutionAdditional proof supports the claimed existence of a PTPC2 superdomain, that is definitely, the inheritance from the two domains a single structural unit. Figure four shows a schematic in the molecular architecture of exemplars of the present set of proteins. A key instance not shown will be the human putative membrane protein EAX08222, in which PTPC2 is at theconserved helix in PTP discussed above. The locations in PTEN of your four novel motifs identified here are shown in Figure 2. Each tends to make a considerable contribution to the domain interface. Lastly, the sequence information also recommend that b strandrich C2 is far more tolerant of turnlength variations than is mixed ab PTP in PTPC2 (see Supporting Facts).Charge properties of PTPCTwo additional points concerning electric charge are worth noting. One, the pI of PTPC2 is standard for each of the animal proteins studied here, regardless 
of divergence from human TNS3 (circles, Fig. three). The plant proteins, by contrast, shown as squares, are about 25 identical to human TNS3 in PTPC2 but are acidic (squares). The physiological significance of these differences is unclear. A distinctive function on the plant proteins is often a formin homology two (FH2) domain downstream of PTPC2. Required for the selfassociation of formin proteins, FH2 also influences actin polymerization in Saccharomyces cerevisiae.three Within the present animal proteins, by contrast,Figure three. Calculated isoelectric point versus nominal percentage identity for the present PTPC2 superdomain sequences. The comparisons have been created with respect to human TNS3. A cyan backgroun.