Molecule Information

General Information of the Molecule (ID: Mol01941)

Name	NPR2 like, GATOR1 complex subunit (NPRL2) ,Homo sapiens
Synonyms	NPRL2; TUSC4 Click to Show/Hide
Molecule Type	Protein
Gene Name	NPRL2
Gene ID	10641
Location	chr3:50,347,330-50,350,826[-]
Sequence	MGSGCRIECIFFSEFHPTLGPKITYQVPEDFISRELFDTVQVYIITKPELQNKLITVTAM EKKLIGCPVCIEHKKYSRNALLFNLGFVCDAQAKTCALEPIVKKLAGYLTTLELESSFVS MEESKQKLVPIMTILLEELNASGRCTLPIDESNTIHLKVIEQRPDPPVAQEYDVPVFTKD KEDFFNSQWDLTTQQILPYIDGFRHIQKISAEADVELNLVRIAIQNLLYYGVVTLVSILQ YSNVYCPTPKVQDLVDDKSLQEACLSYVTKQGHKRASLRDVFQLYCSLSPGTTVRDLIGR HPQQLQHVDERKLIQFGLMKNLIRRLQKYPVRVTREEQSHPARLYTGCHSYDEICCKTGM SYHELDERLENDPNIIICWK Click to Show/Hide
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. Click to Show/Hide
Uniprot ID	NPRL2_HUMAN
Ensembl ID	ENSG00000114388
HGNC ID	HGNC:24969
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

1 drug(s) in total

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Everolimus

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Prostate hyperplasia				[1]
Resistant Disease	Prostate hyperplasia [ICD-11: GA90.0]			Disease Info
Resistant Drug	Everolimus			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	mTOR signaling pathway		Inhibition	hsa04150
In Vitro Model	PC3 cells	Prostate	Homo sapiens (Human)	CVCL_0035
	RWPE-1 cells	Prostate	Homo sapiens (Human)	CVCL_3791
	PCa LNCaP cells	Prostate	Homo sapiens (Human)	CVCL_D575
In Vivo Model	Balb/c athymic nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting assay
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	NPRL2 enhances autophagy and the resistance to Everolimus in castration-resistant prostate cancer.NPRL2-silencing increased the activity of mTOR signaling, and the autophagy attenuation induced by NPRL2-silencing in EVS-treated CRPC cells was associated with the increase of apoptosis.

References

Ref 1	NPRL2 enhances autophagy and the resistance to Everolimus in castration-resistant prostate cancer .Prostate. 2019 Jan;79(1):44-53. doi: 10.1002/pros.23709. Epub 2018 Sep 3. 10.1002/pros.23709