Domain

Myotubularin-like phosphatase domain (IPR010569)

Short name: Myotubularin-like_Pase_dom

Domain relationships

Description

This entry represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate [PMID: 12847286]. Mutations in gene encoding myotubularin-related proteins have been associated with disease [PMID: 12045210].

Myotubularin phosphatases are members of the protein tyrosine phosphatase (PTP) superfamily. The PTP domain is found in a diverse group of enzymes that catalyse phosphoester hydrolysis using a cysteine nucleophile and an arginine residue that binds to oxygen atoms of the phosphate. These two catalytically essential residues are found in a Cys-x(5)-Arg motif, which is a hallmark of PTP domains. The PTP superfamily of enzymes includes tyrosine-specific, dual specificity, low molecular weight, and Cdc25 phosphatases. All of these enzymes utilise phosphoproteins as substrates. Unlike these members of PTPs, enzymes that contain the tensin and myotubularin PTP domain utilise the phosphoinositide as its physiologic substrate. Myotubularins are 3-phosphatases specific for membrane-embedded PtdIns3P and PtdIns(3,5)P2, two PIs that function within the endosomal-lysosomal pathway [PMID: 9818190, PMID: 16828287].

The myotubularin phosphatase domain consists of a central seven stranded beta sheet flanked by thirteen alpha helices [PMID: 14690594]. Although its core structure is similar to that of other PTP superfamily members, the myotubularin phosphatase domain is much larger. It contains an extra C-terminal region, which could be implicated in protein-protein interactions. The active site motif forms a P-loop at the base of a substrate binding pocket that is characteristic of PTP domains. This pocket is significantly deeper than that of other PTP pockets, which could explain the difference in substrate specificity.

The myotubularin family includes catalytically inactive members, or pseudophosphatases, which contain inactivating substitutions in the phosphatase domain [PMID: 16787938].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles
Pfam