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NPRL2 Gene(Protein Coding)

NPR2-Like, GATOR1 Complex Subunit

GCID:
GC03M050384
GIFtS:
52
Genes Participants
UDN Logo

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
  • 2810446G01Rik 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 Lung Cancer. 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, 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.

Gene Wiki entry for NPRL2 Gene

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

Genomics for NPRL2 Gene

Products:

  1. Regulatory Element

Regulatory Elements for NPRL2 Gene

Enhancers for NPRL2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

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

ENSRs around NPRL2 on UCSC Golden Path with GeneCards custom track

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 Structure • Gene Density

RefSeq DNA sequence for NPRL2 Gene

Proteins for NPRL2 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • 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

Proteomics data for NPRL2 Gene at MOPED

Protein Expression for NPRL2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for NPRL2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NPRL2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NPRL2 Gene

Domains & 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

No data available for Gene Families for NPRL2 Gene

Function for NPRL2 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

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. As a component of the GATOR1 complex, 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.

Phenotypes for NPRL2 Gene

GenomeRNAi human phenotypes for NPRL2:
genes like me logo Genes that share phenotypes with NPRL2: view

Animal Model Products

miRNA for NPRL2 Gene

miRTarBase miRNAs that target NPRL2

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for NPRL2 Gene

Localization for NPRL2 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NPRL2 Gene COMPARTMENTS Subcellular localization image for NPRL2 gene
Compartment Confidence
cytosol 4
cytoskeleton 2
nucleus 2
plasma membrane 2
lysosome 1
vacuole 1

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Gene Ontology (GO) - Cellular Components for NPRL2 Gene

Pathways & Interactions for NPRL2 Gene

SuperPathways for NPRL2 Gene

PathCards logoMore details on SuperPathways for NPRL2
No Data Available

Gene Ontology (GO) - Biological Process for NPRL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0033673 negative regulation of kinase activity IDA 18616680
GO:0043547 positive regulation of GTPase activity IEA --
genes like me logo Genes that share ontologies with NPRL2: view

No data available for Pathways by source and SIGNOR curated interactions for NPRL2 Gene

Drugs & Compounds for NPRL2 Gene

Products:

  1. Drug
No Compound Related Data Available

Transcripts for NPRL2 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for NPRL2 Gene

(6) REFSEQ mRNAs :
(12) Additional mRNA sequences :
(236) Selected AceView cDNA sequences:
(17) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NPRL2 Gene

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

Inhibitory RNA Products

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

Products:

  1. Primer

mRNA expression in normal human tissues for NPRL2 Gene

mRNA expression in normal human tissues for NPRL2 Gene
mRNA expression by BioGPS for NPRL2 GenemRNA expression by GTEx 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, MOPED, and MaxQB for NPRL2 Gene



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 most lung cancer cell lines tested.
genes like me logo Genes that share expression patterns with NPRL2: view

Protein tissue co-expression partners for NPRL2 Gene

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues 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
cow
(Bos Taurus)
 Mammalia NPRL2 35
  • 92.37 (n)
  • 97.63 (a)
NPRL2 36
  • 98 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia NPRL2 35
  • 92.63 (n)
  • 98.42 (a)
NPRL2 36
  • 98 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Nprl2 35
  • 89.82 (n)
  • 98.42 (a)
Nprl2 16
Nprl2 36
  • 98 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia NPRL2 35
  • 99.65 (n)
  • 99.74 (a)
NPRL2 36
  • 100 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Nprl2 35
  • 89.39 (n)
  • 98.42 (a)
oppossum
(Monodelphis domestica)
 Mammalia NPRL2 36
  • 95 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia NPRL2 36
  • 90 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves NPRL2 35
  • 79.49 (n)
  • 85.16 (a)
NPRL2 36
  • 89 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia NPRL2 36
  • 89 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia nprl2 35
  • 74.87 (n)
  • 82.35 (a)
African clawed frog
(Xenopus laevis)
 Amphibia nprl2-pending-prov 35
zebrafish
(Danio rerio)
 Actinopterygii nprl2 35
  • 72.56 (n)
  • 82.32 (a)
nprl2 36
  • 82 (a)
 OneToOne
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP000438 35
  • 54.93 (n)
  • 43.82 (a)
fruit fly
(Drosophila melanogaster)
 Insecta CG9104 35
  • 56.18 (n)
  • 46.51 (a)
CG9104 36
  • 42 (a)
 OneToOne
worm
(Caenorhabditis elegans)
 Secernentea nprl-2 35
  • 43.95 (n)
  • 29.36 (a)
nprl-2 36
  • 24 (a)
 OneToOne
A. gosspyii yeast
(Ashbya gossypii)
 Saccharomycetes AGOS_ACR009W 35
  • 46.35 (n)
  • 34.34 (a)
K. lactis yeast
(Kluyveromyces lactis)
 Saccharomycetes KLLA0D01067g 35
  • 44.16 (n)
  • 34.32 (a)
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes NPR2 35
  • 46.03 (n)
  • 36.11 (a)
NPR2 36
  • 19 (a)
 OneToOne
NPR2 38
fission yeast
(Schizosaccharomyces pombe)
 Schizosaccharomycetes npr2 35
  • 43.52 (n)
  • 32.57 (a)
sea squirt
(Ciona savignyi)
 Ascidiacea -- 36
  • 47 (a)
 OneToOne
Species with no ortholog for NPRL2:
  • 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
rs2233483 -- 50,348,634(-) GAAGA(A/C/T)CTCAG intron-variant
rs2233484 -- 50,348,435(-) CAGGC(A/C)CCTAT intron-variant
rs34059532 -- 50,348,221(+) ATCCC(A/C/G)GAGAC nc-transcript-variant, reference, missense
rs34319036 -- 50,348,633(+) CCTGA(-/G)GTCTT intron-variant
rs78491479 -- 50,348,172(+) GGTCT(C/T)GCACG nc-transcript-variant, reference, missense

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

Variant ID Type Subtype PubMed ID
nsv523662 CNV Loss 19592680
nsv876769 CNV Loss 21882294
nsv470561 CNV Loss 18288195
nsv876770 CNV Loss 21882294
nsv834692 CNV Loss 17160897
nsv460531 CNV Loss 19166990
dgv5131n71 CNV Loss 21882294
dgv5132n71 CNV Loss 21882294
nsv834693 CNV Loss 17160897

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)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for NPRL2 Gene

Disorders for NPRL2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for NPRL2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
lung cancer
  • lung cancer, protection against
- 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
  • 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 23 67
  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
  3. 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 23
  4. Functional characterization of the candidate tumor suppressor gene NPRL2/G21 located in 3p21.3C. (PMID: 15374952) Li J. … Zabarovsky E.R. (Cancer Res. 2004) 2 3
  5. TUSC4 functions as a tumor suppressor by regulating BRCA1 stability. (PMID: 25480944) Peng Y. … Lin S.Y. (Cancer Res. 2015) 3

Products for NPRL2 Gene

  • Addgene plasmids for NPRL2

Sources for NPRL2 Gene

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