Phosphatase Subfamily TAB1

Phosphatase Classification: Fold PPM (PP2C): Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily TAB1

Domain

The TAB1 subfamily has a phosphatase domain of PPM fold.

Function

Human TAB1 is a pseudophosphatase but basal metazoa TAB1s are probably active

Human TAB1 is a pseudophosphatase. Several key residues required for dual metal-binding (D69N, D290E, D356E, N367D) and catalysis (H71Y) are substitued by other amino acids [1]. However, not all of the substitutions are conserved in TAB1s. D69 is found in metazoa, such as sponge, nematostella and sea urchin; D290 is found in metazoa except chordates, such as sponge, nematostella and C. elegans; D356 is found in metazoa, such as sponge, nematostella and sea urchin; H71 is found in basal metazoa, such as nematostella and sponge. Thus, TAB1s in basal metazoa are probably active, though human TAB1 is inactive.

TAB1-TAK1 complex

Human TAB1 associated with TAK1 [2]. The association induces TAK1 autoactivation [3].

• TRAF6 [].
• p38α [4, 5, 6]. TAB1 functions as a scaffold protein in the activation of p38 [6]. The interaction between TAB1 and p38α is mediated by Pro-412 on TAB1 and a hydrophobic docking groove on p38α [7]. The Pro-412 of TAB1 does not localize in a conserved region, so it is hard to tell whether it is conserved.

• MEKK1 [8]. TAB1 is ubiquitinated by MEKK1 PHD domain.

Human TAB1 can be dephosphorylated at Ser-452, Ser-453, Ser-456, Ser-457 by TAK1 and p38 [9]. These sites are not found in invertebrates.

References

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