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Protein

GATOR complex protein NPRL3

Gene

NPRL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Caution

Ser-489 is missing in the human genome assembly but is present in all available mRNAs and ESTs.Curated

GO - Molecular functioni

GO - Biological processi

  • aorta morphogenesis Source: Ensembl
  • cardiac muscle tissue development Source: Ensembl
  • cellular response to amino acid starvation Source: UniProtKB
  • negative regulation of TOR signaling Source: SGD
  • regulation of autophagosome assembly Source: GO_Central
  • roof of mouth development Source: Ensembl
  • TORC1 signaling Source: GO_Central
  • ventricular septum development Source: Ensembl

Keywordsi

Molecular functionGTPase activation

Enzyme and pathway databases

SIGNORiQ12980

Names & Taxonomyi

Protein namesi
Recommended name:
GATOR complex protein NPRL3Curated
Alternative name(s):
-14 gene protein1 Publication
Alpha-globin regulatory element-containing gene protein1 Publication
Nitrogen permease regulator 3-like proteinImported
Protein CGTHBA
Gene namesi
Name:NPRL3Imported
Synonyms:C16orf35Imported, CGTHBA, MARE1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103148.15
HGNCiHGNC:14124 NPRL3
MIMi600928 gene
neXtProtiNX_Q12980

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Inactivating mutations and truncating deletions in the genes encoding GATOR1 proteins 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).1 Publication
Epilepsy, familial focal, with variable foci 3 (FFEVF3)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:617118
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07712692R → Q in FFEVF3; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs367729589Ensembl.1
Natural variantiVAR_077127249E → K in FFEVF3; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs200041907Ensembl.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi8131
MalaCardsiNPRL3
MIMi617118 phenotype
OpenTargetsiENSG00000103148
PharmGKBiPA25550

Polymorphism and mutation databases

BioMutaiNPRL3
DMDMi18202492

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206381 – 569GATOR complex protein NPRL3Add BLAST569

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei476PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ12980
MaxQBiQ12980
PaxDbiQ12980
PeptideAtlasiQ12980
PRIDEiQ12980

PTM databases

iPTMnetiQ12980
PhosphoSitePlusiQ12980

Expressioni

Tissue specificityi

Widely expressed. Expressed in the frontal lobe cortex as well as in the temporal, parietal, and occipital lobes (PubMed:27173016, PubMed:26505888).2 Publications

Gene expression databases

BgeeiENSG00000103148
CleanExiHS_C16orf35
ExpressionAtlasiQ12980 baseline and differential
GenevisibleiQ12980 HS

Organism-specific databases

HPAiHPA011741

Interactioni

Subunit structurei

Forms a heterodimer with NPRL2. 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.1 Publication

Protein-protein interaction databases

BioGridi113796, 22 interactors
CORUMiQ12980
DIPiDIP-62051N
IntActiQ12980, 6 interactors
STRINGi9606.ENSP00000382834

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6CESelectron microscopy4.00M1-569[»]
6CETelectron microscopy4.40M1-569[»]
ProteinModelPortaliQ12980
SMRiQ12980
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NPR3 family.Curated

Phylogenomic databases

eggNOGiKOG3830 Eukaryota
ENOG410XP4E LUCA
GeneTreeiENSGT00390000015916
HOGENOMiHOG000004787
HOVERGENiHBG019399
InParanoidiQ12980
KOiK20406
OMAiAHLVYWG
OrthoDBiEOG091G03SH
PhylomeDBiQ12980
TreeFamiTF105965

Family and domain databases

InterProiView protein in InterPro
IPR005365 NPR3
PANTHERiPTHR13153 PTHR13153, 1 hit
PfamiView protein in Pfam
PF03666 NPR3, 2 hits

Sequencei

Sequence statusi: Complete.

Q12980-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRDNTSPISV ILVSSGSRGN KLLFRYPFQR SQEHPASQTS KPRSRYAASN
60 70 80 90 100
TGDHADEQDG DSRFSDVILA TILATKSEMC GQKFELKIDN VRFVGHPTLL
110 120 130 140 150
QHALGQISKT DPSPKREAPT MILFNVVFAL RANADPSVIN CLHNLSRRIA
160 170 180 190 200
TVLQHEERRC QYLTREAKLI LALQDEVSAM ADGNEGPQSP FHHILPKCKL
210 220 230 240 250
ARDLKEAYDS LCTSGVVRLH INSWLEVSFC LPHKIHYAAS SLIPPEAIER
260 270 280 290 300
SLKAIRPYHA LLLLSDEKSL LGELPIDCSP ALVRVIKTTS AVKNLQQLAQ
310 320 330 340 350
DADLALLQVF QLAAHLVYWG KAIIIYPLCE NNVYMLSPNA SVCLYSPLAE
360 370 380 390 400
QFSHQFPSHD LPSVLAKFSL PVSLSEFRNP LAPAVQETQL IQMVVWMLQR
410 420 430 440 450
RLLIQLHTYV CLMASPSEEE PRPREDDVPF TARVGGRSLS TPNALSFGSP
460 470 480 490 500
TSSDDMTLTS PSMDNSSAEL LPSGDSPLNQ RMTENLLASL SEHERAAILS
510 520 530 540 550
VPAAQNPEDL RMFARLLHYF RGRHHLEEIM YNENTRRSQL LMLFDKFRSV
560
LVVTTHEDPV IAVFQALLP
Length:569
Mass (Da):63,605
Last modified:November 1, 1996 - v1
Checksum:i44BEF42AA7F2841D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti489Missing in CAI94885 (PubMed:16728641).Curated1
Sequence conflicti489Missing in CAI95611 (PubMed:16728641).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07712692R → Q in FFEVF3; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs367729589Ensembl.1
Natural variantiVAR_077127249E → K in FFEVF3; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs200041907Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X90857 mRNA Translation: CAA62368.1
DQ431198 Genomic DNA Translation: ABD95907.1
Z69666, Z69720, Z84722 Genomic DNA Translation: CAI94885.1
Z69720, Z69666, Z84722 Genomic DNA Translation: CAI95611.1
CH471112 Genomic DNA Translation: EAW85865.1
CH471112 Genomic DNA Translation: EAW85867.1
CCDSiCCDS73795.1
RefSeqiNP_001070818.1, NM_001077350.2
UniGeneiHs.19699

Genome annotation databases

EnsembliENST00000611875; ENSP00000478273; ENSG00000103148
ENST00000620134; ENSP00000483814; ENSG00000103148
GeneIDi8131
KEGGihsa:8131
UCSCiuc032dmr.2 human

Similar proteinsi

Entry informationi

Entry nameiNPRL3_HUMAN
AccessioniPrimary (citable) accession number: Q12980
Secondary accession number(s): D3DU40
, Q1W6H0, Q4TT56, Q92469
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 1, 1996
Last modified: May 23, 2018
This is version 122 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health