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Aliases for NHLRC1 Gene

Aliases for NHLRC1 Gene

  • NHL Repeat Containing E3 Ubiquitin Protein Ligase 1 2 3
  • EPM2B 3 4 6
  • NHL Repeat-Containing Protein 1 3 4
  • NHL Repeat Containing 1 2 3
  • MALIN 3 4
  • EPM2A 3 6
  • E3 Ubiquitin-Protein Ligase NHLRC1 3
  • Progressive Myoclonus Type 2B 2
  • EC 6.3.2.- 4
  • BA204B7.2 3
  • Epilepsy 2

External Ids for NHLRC1 Gene

Summaries for NHLRC1 Gene

Entrez Gene Summary for NHLRC1 Gene

  • The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]

GeneCards Summary for NHLRC1 Gene

NHLRC1 (NHL Repeat Containing E3 Ubiquitin Protein Ligase 1) is a Protein Coding gene. Diseases associated with NHLRC1 include neuroleptic malignant syndrome and nhlrc1-related lafora disease. Among its related pathways are Metabolism and MPS VI - Maroteaux-Lamy syndrome. GO annotations related to this gene include ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot for NHLRC1 Gene

  • 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.

Gene Wiki entry for NHLRC1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NHLRC1 Gene

Genomics for NHLRC1 Gene

Genomic Location for NHLRC1 Gene

Start:
18,120,487 bp from pter
End:
18,122,620 bp from pter
Size:
2,134 bases
Orientation:
Minus strand

Genomic View for NHLRC1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NHLRC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NHLRC1 Gene

Regulatory Elements for NHLRC1 Gene

Proteins for NHLRC1 Gene

  • Protein details for NHLRC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6VVB1-NHLC1_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase NHLRC1
    Protein Accession:
    Q6VVB1
    Secondary Accessions:
    • Q3SYB1
    • Q5VUK7
    • Q6IMH1

    Protein attributes for NHLRC1 Gene

    Size:
    395 amino acids
    Molecular mass:
    42293 Da
    Quaternary structure:
    • Interacts with AGL. Interacts (via the NHL repeats) with EPM2A/laforin. Forms a complex with EPM2A/laforin and HSP70.

neXtProt entry for NHLRC1 Gene

Proteomics data for NHLRC1 Gene at MOPED

Post-translational modifications for NHLRC1 Gene

No Post-translational modifications

Other Protein References for NHLRC1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for NHLRC1 Gene

Domains for NHLRC1 Gene

Protein Domains for NHLRC1 Gene

UniProtKB/Swiss-Prot:

NHLC1_HUMAN
Domain:
  • The RING domain is essential for ubiquitin E3 ligase activity.:
    • Q6VVB1
Similarity:
  • Contains 6 NHL repeats.:
    • Q6VVB1
  • Contains 1 RING-type zinc finger.:
    • Q6VVB1
genes like me logo Genes that share domains with NHLRC1: view

No data available for Gene Families for NHLRC1 Gene

Function for NHLRC1 Gene

Molecular function for NHLRC1 Gene

UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for NHLRC1 Gene

Gene Ontology (GO) - Molecular Function for NHLRC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IDA 15930137
GO:0005515 protein binding IPI 15930137
GO:0008270 zinc ion binding IEA --
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with NHLRC1: view
genes like me logo Genes that share phenotypes with NHLRC1: view

Animal Models for NHLRC1 Gene

MGI Knock Outs for NHLRC1:

miRNA for NHLRC1 Gene

miRTarBase miRNAs that target NHLRC1

No data available for Transcription Factor Targeting and HOMER Transcription for NHLRC1 Gene

Localization for NHLRC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NHLRC1 Gene

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

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NHLRC1 Gene COMPARTMENTS Subcellular localization image for NHLRC1 gene
Compartment Confidence
endoplasmic reticulum 5
nucleus 5
cytosol 1
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for NHLRC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 17908927
GO:0005783 endoplasmic reticulum IEA --
GO:0005829 cytosol TAS --
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with NHLRC1: view

Pathways for NHLRC1 Gene

genes like me logo Genes that share pathways with NHLRC1: view

Pathways by source for NHLRC1 Gene

1 KEGG pathway for NHLRC1 Gene

UniProtKB/Swiss-Prot Q6VVB1-NHLC1_HUMAN

  • Pathway: Protein modification; protein ubiquitination

Gene Ontology (GO) - Biological Process for NHLRC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IDA 15930137
GO:0005975 carbohydrate metabolic process TAS --
GO:0005978 glycogen biosynthetic process TAS --
GO:0006006 glucose metabolic process TAS --
GO:0006914 autophagy IEA --
genes like me logo Genes that share ontologies with NHLRC1: view

Compounds for NHLRC1 Gene

(1) Novoseek inferred chemical compound relationships for NHLRC1 Gene

Compound -log(P) Hits PubMed IDs
glycogen 56 7
genes like me logo Genes that share compounds with NHLRC1: view

Transcripts for NHLRC1 Gene

mRNA/cDNA for NHLRC1 Gene

(1) REFSEQ mRNAs :
(4) Additional mRNA sequences :
(13) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NHLRC1 Gene

NHL repeat containing 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NHLRC1 Gene

No ASD Table

Relevant External Links for NHLRC1 Gene

GeneLoc Exon Structure for
NHLRC1
ECgene alternative splicing isoforms for
NHLRC1

Expression for NHLRC1 Gene

mRNA expression in normal human tissues for NHLRC1 Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for NHLRC1 Gene

SOURCE GeneReport for Unigene cluster for NHLRC1 Gene Hs.348351

mRNA Expression by UniProt/SwissProt for NHLRC1 Gene

Q6VVB1-NHLC1_HUMAN
Tissue specificity: Expressed in brain, cerebellum, spinal cord, medulla, heart, liver, skeletal muscle and pancreas.
genes like me logo Genes that share expressions with NHLRC1: view

Orthologs for NHLRC1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NHLRC1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NHLRC1 36
  • 99.58 (n)
  • 100 (a)
NHLRC1 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NHLRC1 36
  • 85.67 (n)
  • 88.04 (a)
NHLRC1 37
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NHLRC1 36
  • 86.92 (n)
  • 86.84 (a)
NHLRC1 37
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nhlrc1 36
  • 82.37 (n)
  • 83.77 (a)
Nhlrc1 16
Nhlrc1 37
  • 80 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NHLRC1 37
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NHLRC1 37
  • 54 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nhlrc1 36
  • 81.8 (n)
  • 84.44 (a)
chicken
(Gallus gallus)
Aves NHLRC1 36
  • 62.35 (n)
  • 53.63 (a)
NHLRC1 37
  • 49 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NHLRC1 37
  • 55 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nhlrc1 36
  • 52.65 (n)
  • 46.41 (a)
Species with no ortholog for NHLRC1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for NHLRC1 Gene

ENSEMBL:
Gene Tree for NHLRC1 (if available)
TreeFam:
Gene Tree for NHLRC1 (if available)

Paralogs for NHLRC1 Gene

No data available for Paralogs for NHLRC1 Gene

Variants for NHLRC1 Gene

Sequence variations from dbSNP and Humsavar for NHLRC1 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs6920234 -- 18,124,298(+) tggag(A/T)gcagt upstream-variant-2KB
rs9477631 -- 18,123,541(+) TCACT(A/G)TGTTG upstream-variant-2KB
rs10949480 -- 18,120,793(+) ATTGG(A/G)ACTAA utr-variant-3-prime
rs10949481 -- 18,120,798(+) GACTA(A/T)GGCAG utr-variant-3-prime
rs10949482 -- 18,121,083(+) aagga(C/T)cacct utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for NHLRC1 Gene

Variant ID Type Subtype PubMed ID
nsv830597 CNV Loss 17160897
nsv883460 CNV Gain 21882294

Relevant External Links for NHLRC1 Gene

HapMap Linkage Disequilibrium report
NHLRC1
Human Gene Mutation Database (HGMD)
NHLRC1

Disorders for NHLRC1 Gene

(1) OMIM Diseases for NHLRC1 Gene (608072)

UniProtKB/Swiss-Prot

NHLC1_HUMAN
  • 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:0000269 PubMed:12958597, ECO:0000269 PubMed:15781812, ECO:0000269 PubMed:16021330, ECO:0000269 PubMed:18311786, ECO:0000269 PubMed:21505799}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(6) Novoseek inferred disease relationships for NHLRC1 Gene

Disease -log(P) Hits PubMed IDs
lafora disease 98.3 65
progressive myoclonus epilepsies 96 11
neurodegenerative diseases 50.4 2
neuroleptic malignant syndrome 48.5 2
epilepsy 39.6 3

Relevant External Links for NHLRC1

GeneTests
NHLRC1
GeneReviews
NHLRC1
Genetic Association Database (GAD)
NHLRC1
Human Genome Epidemiology (HuGE) Navigator
NHLRC1
genes like me logo Genes that share disorders with NHLRC1: view

Publications for NHLRC1 Gene

  1. Mutations in NHLRC1 cause progressive myoclonus epilepsy. (PMID: 12958597) Chan E.M. … Scherer S.W. (Nat. Genet. 2003) 2 3 4 23
  2. Lafora disease due to EPM2B mutations: a clinical and genetic study. (PMID: 15781812) Gomez-Abad C. … Serratosa J.M. (Neurology 2005) 3 4 23
  3. Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin. (PMID: 15930137) Gentry M.S. … Dixon J.E. (Proc. Natl. Acad. Sci. U.S.A. 2005) 3 4 23
  4. Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG). (PMID: 18070875) Worby C.A. … Dixon J.E. (J. Biol. Chem. 2008) 3 4 23
  5. Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin. (PMID: 18311786) Singh S. … Ganesh S. (Hum. Mutat. 2008) 3 4 23

Products for NHLRC1 Gene

Sources for NHLRC1 Gene

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