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Aliases for NPRL2 Gene

Aliases for NPRL2 Gene

  • NPR2-Like, GATOR1 Complex Subunit 2 3 5
  • Tumor Suppressor Candidate 4 2 3 4
  • NPR2-Like Protein 3 4
  • Gene 21 Protein 3 4
  • G21 Protein 3 4
  • TUSC4 3 4
  • Homologous To Yeast Nitrogen Permease (Candidate Tumor Suppressor) 3
  • Nitrogen Permease Regulator-Like 2 (S. Cerevisiae) 2
  • Nitrogen Permease Regulator 2-Like Protein 3
  • 2810446G01Rik 3
  • FFEVF2 3
  • NPR2L 3
  • NPR2 3

External Ids for NPRL2 Gene

Previous HGNC Symbols for NPRL2 Gene

  • TUSC4

Summaries for NPRL2 Gene

GeneCards Summary for NPRL2 Gene

NPRL2 (NPR2-Like, GATOR1 Complex Subunit) is a Protein Coding gene. Diseases associated with NPRL2 include Epilepsy, Familial Focal With Variable Foci 2 and Epilepsy, Familial Focal, With Variable Foci. Among its related pathways are mTOR signaling pathway (KEGG). GO annotations related to this gene include protein kinase activity and GTPase activator activity.

UniProtKB/Swiss-Prot for NPRL2 Gene

  • Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at Tyr-9, Tyr-373 and Tyr-376 residues. May act as a tumor suppressor. Suppresses cell growth and enhances sensitivity to various anticancer drugs.

  • As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway.

Gene Wiki entry for NPRL2 Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NPRL2 Gene

Genomics for NPRL2 Gene

Regulatory Elements for NPRL2 Gene

Enhancers for NPRL2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03G050636 0.7 dbSUPER 10.7 -286.0 -286042 0.5 RING1 PHF8 L3MBTL2 RNF2 NRF1 RBBP5 ZNF335 POLR2A BCL6 EZH2 RAD54L2 ENSG00000230454 NPRL2 HEMK1 CISH LINC02019
GH03G050638 0.7 dbSUPER 10.7 -286.1 -286097 0.6 RING1 PHF8 MXI1 L3MBTL2 RNF2 NRF1 BHLHE40 RBBP5 ZNF335 POLR2A RAD54L2 ENSG00000230454 NPRL2 HEMK1 CISH LINC02019
GH03G050637 0.6 dbSUPER 10.7 -286.1 -286053 0.3 RING1 PHF8 L3MBTL2 RNF2 NRF1 ZNF335 POLR2A BCL6 EZH2 ZBTB20 RAD54L2 ENSG00000230454 NPRL2 HEMK1 CISH LINC02019
GH03G050566 2.1 FANTOM5 Ensembl ENCODE dbSUPER 2.5 -220.8 -220813 10.0 CREB3L1 AGO1 DMAP1 YY1 ZNF143 ZNF263 SP3 NFYC TBX21 SSRP1 CISH RAD54L2 SEMA3F-AS1 MAPKAPK3 TMEM115 HEMK1 DOCK3 NAT6 TRAIP RASSF1
GH03G050356 1.1 ENCODE 0.4 -7.1 -7098 4.0 HDGF PKNOX1 MLX CREB3L1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF766 NICN1 CYB561D2 GC03P050359 NPRL2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around NPRL2 on UCSC Golden Path with GeneCards custom track

Promoters for NPRL2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000152349 291 1201 HDGF PKNOX1 MLX CREB3L1 AGO1 ZFP64 WRNIP1 ARID4B SIN3A DMAP1

Genomic Location for NPRL2 Gene

Chromosome:
3
Start:
50,347,330 bp from pter
End:
50,351,091 bp from pter
Size:
3,762 bases
Orientation:
Minus strand

Genomic View for NPRL2 Gene

Genes around NPRL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPRL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NPRL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPRL2 Gene

Proteins for NPRL2 Gene

  • Protein details for NPRL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WTW4-NPRL2_HUMAN
    Recommended name:
    Nitrogen permease regulator 2-like protein
    Protein Accession:
    Q8WTW4
    Secondary Accessions:
    • A8K831
    • Q6FGS2
    • Q9Y249
    • Q9Y497

    Protein attributes for NPRL2 Gene

    Size:
    380 amino acids
    Molecular mass:
    43658 Da
    Quaternary structure:
    • Forms a heterodimer with NPRL3. Interacts with PDPK1. Within the GATOR complex, component of the GATOR1 subcomplex, made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction of the GATOR complex with RRAGA/RRAGC and RRAGB/RRAGC heterodimers.

    Alternative splice isoforms for NPRL2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NPRL2 Gene

Post-translational modifications for NPRL2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for NPRL2 Gene

Domains & Families for NPRL2 Gene

Gene Families for NPRL2 Gene

Protein Domains for NPRL2 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for NPRL2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8WTW4

UniProtKB/Swiss-Prot:

NPRL2_HUMAN :
  • Belongs to the NPR2 family.
Family:
  • Belongs to the NPR2 family.
genes like me logo Genes that share domains with NPRL2: view

Function for NPRL2 Gene

Molecular function for NPRL2 Gene

UniProtKB/Swiss-Prot Function:
Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at Tyr-9, Tyr-373 and Tyr-376 residues. May act as a tumor suppressor. Suppresses cell growth and enhances sensitivity to various anticancer drugs.
UniProtKB/Swiss-Prot Function:
As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway. The GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB within RRAGC-containing heterodimers, thereby deactivating RRAGs, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. The GATOR1 complex is negatively regulated by GATOR2 the other GATOR subcomplex in this amino acid-sensing branch of the TORC1 pathway.

Gene Ontology (GO) - Molecular Function for NPRL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IDA 18616680
GO:0005096 contributes_to GTPase activator activity IDA,IEA 23723238
GO:0005515 protein binding IPI 18616680
genes like me logo Genes that share ontologies with NPRL2: view
genes like me logo Genes that share phenotypes with NPRL2: view

Animal Models for NPRL2 Gene

MGI Knock Outs for NPRL2:

Animal Model Products

CRISPR Products

miRNA for NPRL2 Gene

miRTarBase miRNAs that target NPRL2

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for NPRL2

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NPRL2 Gene

Localization for NPRL2 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NPRL2 gene
Compartment Confidence
lysosome 5
cytosol 4
plasma membrane 2
cytoskeleton 2
nucleus 2

Gene Ontology (GO) - Cellular Components for NPRL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005765 lysosomal membrane IDA 28199306
GO:0005773 vacuole IBA --
GO:1990130 Iml1 complex IDA 23723238
genes like me logo Genes that share ontologies with NPRL2: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for NPRL2 Gene

Pathways & Interactions for NPRL2 Gene

SuperPathways for NPRL2 Gene

SuperPathway Contained pathways
1 mTOR signaling pathway (KEGG)
genes like me logo Genes that share pathways with NPRL2: view

Pathways by source for NPRL2 Gene

1 KEGG pathway for NPRL2 Gene

Gene Ontology (GO) - Biological Process for NPRL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA --
GO:0006995 cellular response to nitrogen starvation IBA --
GO:0010508 positive regulation of autophagy IBA --
GO:0032007 negative regulation of TOR signaling IMP 23723238
GO:0033673 negative regulation of kinase activity IDA 18616680
genes like me logo Genes that share ontologies with NPRL2: view

No data available for SIGNOR curated interactions for NPRL2 Gene

Transcripts for NPRL2 Gene

Unigene Clusters for NPRL2 Gene

Nitrogen permease regulator-like 2 (S. cerevisiae):
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for NPRL2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NPRL2 Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10a · 10b ^ 11 ^ 12
SP1: - - - - -
SP2: - - - -
SP3: - - - - - -
SP4: - -
SP5: - - - - -
SP6: - - - - -
SP7: - - - - - -
SP8: -
SP9:
SP10: - - - -
SP11: - - - - -
SP12:
SP13: - -
SP14: -
SP15: - -
SP16: -
SP17:

Relevant External Links for NPRL2 Gene

GeneLoc Exon Structure for
NPRL2
ECgene alternative splicing isoforms for
NPRL2

Expression for NPRL2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NPRL2 Gene

Protein differential expression in normal tissues from HIPED for NPRL2 Gene

This gene is overexpressed in Placenta (15.0), Frontal cortex (13.5), Blymphocyte (12.9), Testis (9.7), and Ovary (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for NPRL2 Gene



Protein tissue co-expression partners for NPRL2 Gene

NURSA nuclear receptor signaling pathways regulating expression of NPRL2 Gene:

NPRL2

SOURCE GeneReport for Unigene cluster for NPRL2 Gene:

Hs.437083

mRNA Expression by UniProt/SwissProt for NPRL2 Gene:

Q8WTW4-NPRL2_HUMAN
Tissue specificity: Most abundant in skeletal muscle, followed by brain, liver and pancreas, with lower amounts in lung, kidney, placenta and heart. Expressed in the frontal lobe cortex as well as in the temporal, parietal, and occipital lobes (PubMed:27173016, PubMed:26505888). Expressed in most lung cancer cell lines tested.

Evidence on tissue expression from TISSUES for NPRL2 Gene

  • Intestine(4.4)
  • Kidney(4.2)
  • Skin(4.2)
  • Nervous system(4)
genes like me logo Genes that share expression patterns with NPRL2: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for NPRL2 Gene

Orthologs for NPRL2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NPRL2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NPRL2 35 34
  • 99.65 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NPRL2 35
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NPRL2 35 34
  • 92.63 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NPRL2 35 34
  • 92.37 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NPRL2 35
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nprl2 16 35 34
  • 89.82 (n)
rat
(Rattus norvegicus)
Mammalia Nprl2 34
  • 89.39 (n)
chicken
(Gallus gallus)
Aves NPRL2 35 34
  • 79.49 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NPRL2 35
  • 89 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nprl2 34
  • 74.87 (n)
African clawed frog
(Xenopus laevis)
Amphibia nprl2-pending-prov 34
zebrafish
(Danio rerio)
Actinopterygii nprl2 35 34
  • 72.56 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG9104 34 35
  • 56.18 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000438 34
  • 54.93 (n)
worm
(Caenorhabditis elegans)
Secernentea nprl-2 34 35
  • 43.95 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR009W 34
  • 46.35 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NPR2 34 35 37
  • 46.03 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D01067g 34
  • 44.16 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 47 (a)
OneToOne
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes npr2 34
  • 43.52 (n)
Species where no ortholog for NPRL2 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • 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)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • 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 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)

Evolution for NPRL2 Gene

ENSEMBL:
Gene Tree for NPRL2 (if available)
TreeFam:
Gene Tree for NPRL2 (if available)

Paralogs for NPRL2 Gene

No data available for Paralogs for NPRL2 Gene

Variants for NPRL2 Gene

Sequence variations from dbSNP and Humsavar for NPRL2 Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs149128231 Epilepsy, familial focal, with variable foci 2 (FFEVF2) [MIM:617116] 50,348,728(+) CACAT(C/G)TGCCT nc-transcript-variant, upstream-variant-2KB, reference, missense
rs745518585 Epilepsy, familial focal, with variable foci 2 (FFEVF2) [MIM:617116] 50,348,775(+) TGTAG(G/T)GCAGG nc-transcript-variant, upstream-variant-2KB, reference, missense
VAR_077122 Epilepsy, familial focal, with variable foci 2 (FFEVF2) [MIM:617116]
VAR_077123 Epilepsy, familial focal, with variable foci 2 (FFEVF2) [MIM:617116]
rs886037963 Pathogenic 50,350,001(-) TCTCC(C/T)GAGAG nc-transcript-variant, upstream-variant-2KB, reference, synonymous-codon, stop-gained, utr-variant-5-prime

Structural Variations from Database of Genomic Variants (DGV) for NPRL2 Gene

Variant ID Type Subtype PubMed ID
dgv8317n54 CNV loss 21841781
esv3584502 CNV gain 24956385
nsv460531 CNV loss 19166990
nsv470561 CNV loss 18288195
nsv473620 CNV novel sequence insertion 20440878
nsv523662 CNV loss 19592680
nsv590255 CNV loss 21841781
nsv834692 CNV loss 17160897
nsv834693 CNV loss 17160897
nsv954855 CNV deletion 24416366

Variation tolerance for NPRL2 Gene

Residual Variation Intolerance Score: 15.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.43; 9.50% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NPRL2 Gene

Human Gene Mutation Database (HGMD)
NPRL2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NPRL2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NPRL2 Gene

Disorders for NPRL2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for NPRL2 Gene - From: ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
epilepsy, familial focal with variable foci 2
  • ffevf2
epilepsy, familial focal, with variable foci
  • familial focal epilepsy with variable foci
focal epilepsy
  • localisation-related epilepsy
- elite association - COSMIC cancer census association via MalaCards
Search NPRL2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NPRL2_HUMAN
  • Epilepsy, familial focal, with variable foci 2 (FFEVF2) [MIM:617116]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete. {ECO:0000269 PubMed:26505888, ECO:0000269 PubMed:27173016}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins, including NPRL2, are detected in glioblastoma and ovarian tumors and are associated with loss of heterozygosity events. Inactivation of GATOR1 proteins promotes constitutive localization of mTORC1 to the lysosomal membrane and blocks mTORC1 inactivation following amino acid withdrawal (PubMed:23723238). {ECO:0000269 PubMed:23723238}.

Relevant External Links for NPRL2

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NPRL2
genes like me logo Genes that share disorders with NPRL2: view

No data available for Genatlas for NPRL2 Gene

Publications for NPRL2 Gene

  1. TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine phosphorylation and its downstream signaling. (PMID: 18616680) Kurata A. … Fujita N. (Cancer Sci. 2008) 2 3 4 22 64
  2. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. (PMID: 23723238) Bar-Peled L. … Sabatini D.M. (Science 2013) 2 3 4 64
  3. Mutations in the mTOR pathway regulators NPRL2 and NPRL3 cause focal epilepsy. (PMID: 26505888) Ricos M.G. … Dibbens L.M. (Ann. Neurol. 2015) 3 4 64
  4. Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer. (PMID: 20193080) Senchenko V.N. … Zabarovsky E.R. (BMC Cancer 2010) 3 22 64
  5. A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex. (PMID: 19521502) Neklesa T.K. … Davis R.W. (PLoS Genet. 2009) 3 4 64

Products for NPRL2 Gene

Sources for NPRL2 Gene

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