“NPRL3”的意思、由来-开放百科全书

NPRL3 is a human protein of poorly understood function^[2] but has been associated with cancer.

The most prominent function ascribed to Nprl3 to date is as part of the GATOR1 complex^[3] (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.^[2] 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.^[4]

Gene

In Homo sapiens, the NPRL3 gene is located at C16orf35. The gene is composed of 14 exons at 53 kbp in length.^[5] This gene is highly conserved in vertebrates^[6] 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.^[2]

Structure

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.^[7] These regions are predicted bind to another macromolecule, which could be DNA, RNA or protein.

References

1. ^{{cite web | title = Entrez Gene: Nitrogen permease regulator-like 3 (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/gene/8131 }}
2. ^¹²{{cite journal | vauthors = 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 | title = Nprl3 is required for normal development of the cardiovascular system | journal = Mamm. Genome | volume = 23 | issue = 7-8 | pages = 404–15 | year = 2012 | pmid = 22538705 | doi = 10.1007/s00335-012-9398-y }}
3. ^{{cite journal | vauthors = Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM | title = A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 | journal = Science | volume = 340 | issue = 6136 | pages = 1100–6 | date = May 2013 | pmid = 23723238 | pmc = 3728654 | doi = 10.1126/science.1232044 }}
4. ^{{cite web|last1=Youheng|first1=Wei|title=The Drosophila Nprl2/Nprl3 complex controls the response to nutrient stress by modulating TORC1 activity|url=https://www.training.nih.gov/assets/FARE2015_winners_by_study_section.pdf|website=National Institute of Health|publisher=NICHD|accessdate=19 March 2015}}
5. ^{{cite journal | vauthors = Lunardi A, Chiacchiera F, D'Este E, Carotti M, Dal Ferro M, Di Minin G, Del Sal G, Collavin L | title = The evolutionary conserved gene C16orf35 encodes a nucleo-cytoplasmic protein that interacts with p73 | journal = Biochem. Biophys. Res. Commun. | volume = 388 | issue = 2 | pages = 428–33 | year = 2009 | pmid = 19666006 | doi = 10.1016/j.bbrc.2009.08.027 }}
6. ^{{cite journal | vauthors = Hughes JR, Cheng JF, Ventress N, Prabhakar S, Clark K, Anguita E, De Gobbi M, de Jong P, Rubin E, Higgs DR | title = Annotation of cis-regulatory elements by identification, subclassification, and functional assessment of multispecies conserved sequences | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 102 | issue = 28 | pages = 9830–5 | year = 2005 | pmid = 15998734 | pmc = 1174996 | doi = 10.1073/pnas.0503401102 }}
7. ^{{cite journal | vauthors = Zhang D, Iyer LM, He F, Aravind L | title = Discovery of Novel DENN Proteins: Implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease | journal = Front Genet | volume = 3 | issue = | pages = 283 | year = 2012 | pmid = 23248642 | pmc = 3521125 | doi = 10.3389/fgene.2012.00283 }}

Function

Gene

Structure

Domains

References