Phosphatase Subfamily DSP23

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP23

summary...

Evolution

Laforin found in vertebrates and scattered other species. It has a single human member, EPM2A.

Domain

Laforin has two domains: carbohydrate-binding module and phosphatase domain. The carbohydrate-binding module targets laforin to Lafora inclusion bodies [1, 2]. The phosphatase domain can directly dephosphorylates glycogen [3, 4]. Epilepsy-caused mutations are found on both domains.

Function

Laforin is a glucan phosphatase [3, 4].

laforin is also a phosphatase of muscle glycogen synthase (GS1) in polyglucosan bodies (PBs). In Lafora disease (LD), the deficiency of either laforin or E3 ligase malin causes massive accumulation of less-branched glycogen inclusions, known as Lafora bodies, also called polyglucosan bodies (PBs), in several types of cells including neurons. Once GS1-synthesized polyglucosan accumulates into PBs, laforin recruits malin to the PBs where laforin dephosphorylates, and malin degrades the GS1 in concert with GPBB and AGL1, resulting in a breakdown of polyglucosan [5]. Laforin also dephosphorylates Ser 9 of Glycogen synthase kinase 3 [6].

Laforin also as an adaptor protein involved in several physiological pathways [7]. For instance, the complex of laforin and malin modules protein phosphatase 1 regulatory subunit PPP1R3D via ubiquitination [8]. See [7] for details.