EC Number   |
General Information |
Reference |
|---|
   3.1.3.56 | evolution |
enzyme Siw14 is a member of the protein tyrosine-phosphatase (PTP) superfamily. Siw14 has a cysteine-based, class I CX5R(S/T) motif that defines the family of protein-tyrosine phosphatases (PTPs). Bioinformatic studies lead to Siw14 being classified as belonging within a specialist subgroup of PTPs, the dual specific protein-tyrosine phosphatases (DUSPs). The DUSPs themselves include a distinct class of proteins that appears not to have substantial activity against phosphoproteins. These are usually described as nonprotein-specific or atypical phosphatases. The inclusion of Siw14 in this category is supported by biochemical analysis, the enzyme's catalytic activity against 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) is several orders of magnitude greater than that against 4-nitrophenyl phosphate, a generic protein phosphatase substrate. Other members of this atypical DUSP subgroup preferentially hydrolyze either phosphorylated carbohydrates, inositol lipids, or triphosphate groups in mRNA. Thus, this DUSP subfamily exhibits catalytic site diversity that is not observed for classical PTPs |
-, 751120 |
| 3.1.3.56 | malfunction |
the increase in the levels of 1D-myo-inositol 1,4,5-trisphosphate/Ca2+ caused by deficiency of inositol polyphosphate 5-phosphatases is sufficient to break pollen dormancy and to trigger early germination |
729621 |
| 3.1.3.56 | metabolism |
inositol pyrophosphate metabolism in Saccharomyces cerevisiae involving enzyme Siw14, overview |
-, 751120 |
| 3.1.3.56 | more |
active site architecture and substrate binding pocket structure, overview. The core catalytic domain of Siw14 is formed by residues 116-281. The three structural elements that demarcate a 9.2-A-deep substrate-binding pocket each have spatial equivalents in PTPs, but these are specialized for Siw14 to bind and hydrolyze the intensely negatively charged diphosphoinositol phosphates. A loop between the alpha5 and alpha6 helices, corresponding to the Q-loop in PTPs, contains a lysine and an arginine that extend into the catalytic pocket due to displacement of the alpha5 helix orientation through intramolecular crowding caused by three bulky, hydrophobic residues. The general-acid loop in PTPs is replaced in Siw14 with a flexible loop that does not use an aspartate or glutamate as a general acid |
-, 751120 |
| 3.1.3.56 | physiological function |
downregulation of INPP5K disrupts muscle fiber morphology and results in abnormal eye development |
749530 |
| 3.1.3.56 | physiological function |
mutations of the isoform SHIP2 result in defects in insulin signaling and obesity |
730981 |
| 3.1.3.56 | physiological function |
SHIP2 plays a role in negative regulation of insulin signaling and as a potential drug target for obesity and type 2 diabetes |
730984 |
| 3.1.3.56 | physiological function |
the enzyme is crucial for maintaining pollen dormancy |
729621 |
| 3.1.3.56 | physiological function |
the enzyme links endoplasmic reticulum stress to insulin resistance in skeletal muscle |
751561 |
