InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NHLRC1

Summary

InnateDB Protein

IDBP-63833.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NHLRC1

Protein Name

NHL repeat containing 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000345464

InnateDB Gene

IDBG-63831 (NHLRC1)

Protein Structure

UniProt Annotation

Function

E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Also promotes proteasome-independent protein degradation through the macroautophagy pathway. {ECO:0000269PubMed:15930137, ECO:0000269PubMed:17908927, ECO:0000269PubMed:18070875, ECO:0000269PubMed:19036738, ECO:0000269PubMed:21505799, ECO:0000269PubMed:23624058}.

Subcellular Localization

Endoplasmic reticulum. Nucleus. Note=Localizes at the endoplasmic reticulum and, to a lesser extent, in the nucleus.

Disease Associations

Epilepsy, progressive myoclonic 2 (EPM2) [MIM:254780]: An autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum. {ECO:0000269PubMed:12958597, ECO:0000269PubMed:15781812, ECO:0000269PubMed:16021330, ECO:0000269PubMed:18311786, ECO:0000269PubMed:21505799}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in brain, cerebellum, spinal cord, medulla, heart, liver, skeletal muscle and pancreas. {ECO:0000269PubMed:12958597}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 26 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	26 [view]
Protein-Protein	26 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity

Biological Process

GO:0000209	protein polyubiquitination
GO:0005975	carbohydrate metabolic process
GO:0005978	glycogen biosynthetic process
GO:0006006	glucose metabolic process
GO:0006914	autophagy
GO:0031398	positive regulation of protein ubiquitination
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0044281	small molecule metabolic process