Difference between revisions of "Phosphatase Subfamily Laforin"
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_Laforin|Subfamily Laforin]] | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_Laforin|Subfamily Laforin]] | ||
| − | Laforin is a | + | Laforin is a [http://en.wikipedia.org/wiki/Glucan glucan] phosphatase and an adaptor protein. |
=== Evolution === | === Evolution === | ||
| − | Laforin found in vertebrates, ciliates, alveolates and plants as well as a few additional species including the animals Trichinella (nematode), Branchiostoma (lancelet) and Nematostella (anemone). It has a single human member, EPM2A. | + | Laforin found in vertebrates, ciliates, alveolates and plants as well as a few scattered additional species including the animals Trichinella (nematode), Branchiostoma (lancelet) and Nematostella (anemone). It has a single human member, EPM2A. |
=== Domain === | === Domain === | ||
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=== Function === | === Function === | ||
| − | Laforin is a glucan phosphatase <cite>Worby06, Gentry07</cite> | + | Laforin is a glucan phosphatase <cite>Worby06, Gentry07</cite> and a phosphatase of muscle glycogen synthase (GS1) in polyglucosan bodies (PBs). |
| − | + | In [http://en.wikipedia.org/wiki/Lafora_disease Lafora disease] (LD), the deficiency of either laforin or the E3 ligase malin causes massive accumulation of less-branched glycogen inclusions, known as [http://en.wikipedia.org/wiki/Lafora_disease#Lafora_bodies 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 <cite>Liu14</cite>. | |
| − | + | ||
| − | In [http://en.wikipedia.org/wiki/Lafora_disease Lafora disease] (LD), the deficiency of either laforin or E3 ligase malin causes massive accumulation of less-branched glycogen inclusions, known as [http://en.wikipedia.org/wiki/Lafora_disease#Lafora_bodies 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 <cite>Liu14</cite>. | + | |
Laforin also dephosphorylates Ser 9 of Glycogen synthase kinase 3 <cite>Lohi05</cite>. | Laforin also dephosphorylates Ser 9 of Glycogen synthase kinase 3 <cite>Lohi05</cite>. | ||
| − | Laforin also as an adaptor protein involved in several physiological pathways <cite>Gentry13</cite>. For instance, the complex of laforin and malin modules protein phosphatase 1 regulatory subunit PPP1R3D via ubiquitination <cite>Rubio-Villena13</cite>. See <cite>Gentry13</cite> for details. | + | Laforin also serves as an adaptor protein involved in several physiological pathways <cite>Gentry13</cite>. For instance, the complex of laforin and malin modules protein phosphatase 1 regulatory subunit PPP1R3D via ubiquitination <cite>Rubio-Villena13</cite>. See <cite>Gentry13</cite> for details. |
| + | |||
| + | DSP4/SEX4 is one of several plant Laforins, and is implicated in breakdown of starch in the chloroplast <cite>Kotting<cite>, as is another family member, LSF2 <cite>Santelia<cite>, while LSF1 is predicted to be an inactive scaffold <cite>Silver</cite> | ||
=== References === | === References === | ||
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#Gentry07 pmid=17646401 | #Gentry07 pmid=17646401 | ||
#Gentry13 pmid=22364389 | #Gentry13 pmid=22364389 | ||
| + | #Kotting pmid=19141707 | ||
#Liu06 pmid=16971387 | #Liu06 pmid=16971387 | ||
#Liu14 pmid=24068615 | #Liu14 pmid=24068615 | ||
#Lohi05 pmid=16115820 | #Lohi05 pmid=16115820 | ||
#Rubio-Villena13 pmid=23624058 | #Rubio-Villena13 pmid=23624058 | ||
| + | #Santelia pmid=22100529 | ||
| + | #Silver pmid=24534096 | ||
#Wang02 pmid=11739371 | #Wang02 pmid=11739371 | ||
#Worby06 pmid=16901901 | #Worby06 pmid=16901901 | ||
</biblio> | </biblio> | ||
Revision as of 04:34, 30 April 2015
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily Laforin
Laforin is a glucan phosphatase and an adaptor protein.
Evolution
Laforin found in vertebrates, ciliates, alveolates and plants as well as a few scattered additional species including the animals Trichinella (nematode), Branchiostoma (lancelet) and Nematostella (anemone). It has a single human member, EPM2A.
Domain
Laforin typically has an N-terminal CBM20 carbohydrate-binding module and a C-terminal phosphatase domain. The carbohydrate-binding module targets laforin to Lafora inclusion bodies [1, 2]. The phosphatase domain directly dephosphorylates glycogen [3, 4]. Multiple plant homologs lack the CBM20 domain. Epilepsy-caused mutations are found on both domains.
Function
Laforin is a glucan phosphatase [3, 4] and a phosphatase of muscle glycogen synthase (GS1) in polyglucosan bodies (PBs). In Lafora disease (LD), the deficiency of either laforin or the 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 serves 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.
DSP4/SEX4 is one of several plant Laforins, and is implicated in breakdown of starch in the chloroplast [9, 10, 10, 10, 10, 11, 12, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]
References
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