Recombinant Human E3 ubiquitin-protein ligase NHLRC1 (NHLRC1)

1. Malin promotes its own degradation via auto-ubiquitination.Malin preferentially degrades the phosphatase-inactive laforin monomer. PMID: 26648032
2. laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2 PMID: 26493215
3. Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway. PMID: 26102034
4. This study demonistrated that NHLRC1 mutations were detected in some case of Mild Lafora disease patients. PMID: 25270369
5. Without functional laforin-malin complex assembled on polyglucosan bodies, polyglucosan is not degraded. PMID: 24068615
6. Malin regulates the recruitment of mRNA-decapping enzyme 1A (Dcp1a) to processing bodies. PMID: 23131811
7. Malin forms a functional complex with laforin. This complex promotes the ubiquitination of proteins involved in glycogen metabolism and misregulation of pathways involved in this process results in Lafora body formation. (Review) PMID: 22815132
8. This study identified that NHLRC1 gene mutations leading to Lafora disease in six Turkish families. PMID: 22047982
9. Our results indicate that malin regulates Wnt signaling pathway through the degradation of dishevelled2 and suggest possible deregulation of Wnt signaling in Lafora disease. PMID: 22223637
10. Mutations in the NHL repeat containing 1 (NHLRC1) gene are described in association with a more benign clinical course and later age of death in an adolescent patient. PMID: 21555062
11. Laforin and malin are defective in Lafora disease (LD), a neurodegenerative disorder associated with epileptic seizures PMID: 21652633
12. malin(C46Y), malin(P69A), malin(D146N), and malin(L261P) mutants failed to downregulate the level of R5/PTG, a regulatory subunit of protein phosphatase 1 involved in glycogen synthesis. PMID: 21505799
13. malin negatively regulates neuronatin and its loss of function in Lafora disease results in increased accumulation of neuronatin PMID: 21742036
14. Malin is related to TRIM32 at both the phylogenetic and functional level. PMID: 21798009
15. study described several novel mutations of EPM2A and NHLRC1 and brought additional data to genetic epidemiology of Lafora disease (LD); emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy PMID: 20738377
16. These results suggest that the modification introduced by the laforin-malin complex could affect the subcellular distribution of AMPK beta subunits. PMID: 20534808
17. the co-chaperone carboxyl terminus of the Hsc70-interacting protein (CHIP) stabilizes malin by modulating the activity of Hsp70. PMID: 19892702
18. Laforin and malin colocalize to the ER, suggesting they operate in a related pathway protecting against polyglucosan accumulation and epilepsy PMID: 12958597
19. Genetic allelic heterogeneity is present in Lafora disease associated with mutations in EPM2B. Patients with mutations in EPM2A and EPM2B express similar clinical manifestation. PMID: 15781812
20. Malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin. PMID: 15930137
21. Malin is an E3 ubiquitin ligase that binds glycogen synthase. PMID: 16115820
22. Patients with NHLRC1 mutations have a slower rate of disease progression than those with EPM2A mutations. PMID: 16950819
23. Defects in malin may lead to increased levels of misfolded and/or target proteins, which may eventually affect the physiological processes of the neuron, and likely to be the primary trigger in the physiopathology of lafora disease. PMID: 17337485
24. Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase complex pathway. PMID: 18029386
25. malin ubiquitinates PTG in a laforin-dependent manner, both in vivo and in vitro, and targets PTG for proteasome-dependent degradation. These results suggest an additional mechanism, involving laforin and malin, in regulating glycogen metabolism PMID: 18070875
26. The authors identified 14 Lafora epilepsy patients in the genetic isolate of tribal Oman. The authors show that in this homogeneous environment and gene pool, the same mutation, EPM2B-c.468-469delAG, results in highly uniform ages of onset and death. PMID: 18263761
27. Results suggest that the altered subcellular localization of mutant proteins of the EPM2A and NHLRC1 genes could be one of the molecular bases of the Lafora disease phenotype. PMID: 18311786
28. Laforin and malin interact with misfolded proteins and promote their degradation through the ubiquitin-proteasome system. PMID: 19036738
29. phosphorylation of R5/PTG at Ser-8 by AMPK accelerates its laforin/malin-dependent ubiquitination and subsequent proteasomal degradation, which results in a decrease of its glycogenic activity. PMID: 19171932
30. Results describe a novel homozygous single-nucleotide variant in the NHLRC1 gene in a Malian consanguineous family. PMID: 19322595
31. laforin and malin play a role protecting cells from ER-stress, likely contributing to the elimination of unfolded proteins PMID: 19529779
32. Meta-analysis of gene-disease association. (HuGE Navigator) PMID: 19267391
33. The phosphatase laforin acts as a scaffold that allows malin to ubiquitinate protein targeting to glycogen (PTG). These results suggest an additional mechanism, involving laforin and malin, in regulating glycogen metabolism. PMID: 18070875

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HGNC: 21576

OMIM: 254780

KEGG: hsa:378884

STRING: 9606.ENSP00000345464

UniGene: Hs.348351