NPRL3

NPRL3
Identifiers
Aliases NPRL3, C16orf35, CGTHBA, HS-40, MARE, NPR3, RMD11, NPR3 like, GATOR1 complex subunit
External IDs MGI: 109258 HomoloGene: 8091 GeneCards: NPRL3
Genetically Related Diseases
sickle cell anemia[1]
Orthologs
Species Human Mouse
Entrez

8131

17168

Ensembl

ENSG00000103148

ENSMUSG00000020289

UniProt

Q12980

Q8VIJ8

RefSeq (mRNA)

NM_001284359
NM_001284360
NM_181569

RefSeq (protein)

NP_001070818.1

NP_001271288.1
NP_001271289.1
NP_853547.1

Location (UCSC) Chr 16: 0.08 – 0.14 Mb Chr 11: 32.23 – 32.27 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

Nitrogen permease regulator-like 3 is a protein that in humans is encoded by the NPRL3 gene.[4]

Function

NPRL3 is a human protein of poorly understood function[5] but has been associated with cancer.

The most prominent function ascribed to Nprl3 to date is as part of the GATOR1 complex[6] (with NPRL2 and DEPDC5) that inhibits the mechanistic target of rapamycin (mTOR) kinase-complex-1 (mTORC1) on the surface of the lysosome (equivalent of degradative vacuole in yeast) via an effect on the Rag GTPase complex. Additionally, Nprl3 has been shown to adjust cell metabolism via the TOR pathway, and this is important for development of the cardiovascular system in mammals.[5] Without this effect, spontaneous cell apoptosis would occur. A similar function for Nprl3 has been identified in the female reproductive system of Drosophila during times of protein scarcity.[7]

Gene

In Homo sapiens, the NPRL3 gene is located at C16orf35. The gene is composed of 14 exons at 53 kbp in length.[8] This gene is highly conserved in vertebrates[9] which is upstream from the alpha globin gene cluster. Within the fifth intron of the gene there is a regulatory section of DNA HS-40 which regulates the expression of the alpha globin. This means that the gene C16orf35 is expressed in early erythrocytes accompanying hemoglobin production.[5]

Structure

The human nitrogen permease regulator-like 3 protein has 569 amino acids.

Domains

There is a predicted N-terminal longin domain within the Nprl3 protein (amino acids 4-168). At the C terminus there are three consecutive winged helix turn helix (HTH) domains.[10] These regions are predicted bind to another macromolecule, which could be DNA, RNA or protein.

References

  1. ↑ "Diseases that are genetically associated with NPRL3 view/edit references on wikidata".
  2. ↑ "Human PubMed Reference:".
  3. ↑ "Mouse PubMed Reference:".
  4. ↑ "Entrez Gene: Nitrogen permease regulator-like 3 (S. cerevisiae)".
  5. 1 2 3 Kowalczyk MS, Hughes JR, Babbs C, Sanchez-Pulido L, Szumska D, Sharpe JA, Sloane-Stanley JA, Morriss-Kay GM, Smoot LB, Roberts AE, Watkins H, Bhattacharya S, Gibbons RJ, Ponting CP, Wood WG, Higgs DR (2012). "Nprl3 is required for normal development of the cardiovascular system". Mamm. Genome. 23 (7-8): 404–15. doi:10.1007/s00335-012-9398-y. PMID 22538705.
  6. ↑ Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM (May 2013). "A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1". Science. 340 (6136): 1100–6. doi:10.1126/science.1232044. PMC 3728654Freely accessible. PMID 23723238.
  7. ↑ Youheng, Wei. "The Drosophila Nprl2/Nprl3 complex controls the response to nutrient stress by modulating TORC1 activity" (PDF). National Institute of Health. NICHD. Retrieved 19 March 2015.
  8. ↑ Lunardi A, Chiacchiera F, D'Este E, Carotti M, Dal Ferro M, Di Minin G, Del Sal G, Collavin L (2009). "The evolutionary conserved gene C16orf35 encodes a nucleo-cytoplasmic protein that interacts with p73". Biochem. Biophys. Res. Commun. 388 (2): 428–33. doi:10.1016/j.bbrc.2009.08.027. PMID 19666006.
  9. ↑ Hughes JR, Cheng JF, Ventress N, Prabhakar S, Clark K, Anguita E, De Gobbi M, de Jong P, Rubin E, Higgs DR (2005). "Annotation of cis-regulatory elements by identification, subclassification, and functional assessment of multispecies conserved sequences". Proc. Natl. Acad. Sci. U.S.A. 102 (28): 9830–5. doi:10.1073/pnas.0503401102. PMC 1174996Freely accessible. PMID 15998734.
  10. ↑ Zhang D, Iyer LM, He F, Aravind L (2012). "Discovery of Novel DENN Proteins: Implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease". Front Genet. 3: 283. doi:10.3389/fgene.2012.00283. PMC 3521125Freely accessible. PMID 23248642.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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