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UniProtKB - Q8WTW4 (NPRL2_HUMAN)

Protein

GATOR complex protein NPRL2

Gene

NPRL2

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
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.1 Publication

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB-KW
  • protein kinase activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGTPase activation

Enzyme and pathway databases

SIGNORiQ8WTW4

Names & Taxonomyi

Protein namesi
Recommended name:
GATOR complex protein NPRL2Curated
Alternative name(s):
Gene 21 protein1 Publication
Short name:
G21 protein1 Publication
Nitrogen permease regulator 2-like protein1 Publication
Short name:
NPR2-like protein1 Publication
Tumor suppressor candidate 41 Publication
Gene namesi
Name:NPRL2Imported
Synonyms:TUSC41 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114388.12
HGNCiHGNC:24969 NPRL2
MIMi607072 gene
neXtProtiNX_Q8WTW4

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, 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).1 Publication
Epilepsy, familial focal, with variable foci 2 (FFEVF2)2 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:617116
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077122105L → P in FFEVF2. 1 PublicationCorresponds to variant dbSNP:rs886037965EnsemblClinVar.1
Natural variantiVAR_077123110T → S in FFEVF2; unknown pathological significance. 1 Publication1
Natural variantiVAR_077124198P → H in FFEVF2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs745518585Ensembl.1
Natural variantiVAR_077125214D → H in FFEVF2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs149128231Ensembl.1

Keywords - Diseasei

Disease mutation, Epilepsy, Tumor suppressor

Organism-specific databases

DisGeNETi10641
MalaCardsiNPRL2
MIMi617116 phenotype
OpenTargetsiENSG00000114388
Orphaneti98820 Familial focal epilepsy with variable foci
PharmGKBiPA165697981

Polymorphism and mutation databases

BioMutaiNPRL2
DMDMi47117604

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002133191 – 380GATOR complex protein NPRL2Add BLAST380

Proteomic databases

EPDiQ8WTW4
MaxQBiQ8WTW4
PaxDbiQ8WTW4
PeptideAtlasiQ8WTW4
PRIDEiQ8WTW4
ProteomicsDBi74610
74611 [Q8WTW4-2]

PTM databases

iPTMnetiQ8WTW4
PhosphoSitePlusiQ8WTW4

Expressioni

Tissue specificityi

Most abundant in skeletal muscle, followed by brain, liver and pancreas, with lower amounts in lung, kidney, placenta and heart. Expressed in the frontal lobe cortex as well as in the temporal, parietal, and occipital lobes (PubMed:27173016, PubMed:26505888). Expressed in most lung cancer cell lines tested.2 Publications

Gene expression databases

BgeeiENSG00000114388 Expressed in 112 organ(s), highest expression level in cerebellar hemisphere
CleanExiHS_TUSC4
ExpressionAtlasiQ8WTW4 baseline and differential
GenevisibleiQ8WTW4 HS

Organism-specific databases

HPAiHPA038196
HPA038197

Interactioni

Subunit structurei

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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NPRL3Q129805EBI-1043552,EBI-2650314

Protein-protein interaction databases

BioGridi115885, 19 interactors
CORUMiQ8WTW4
DIPiDIP-50746N
IntActiQ8WTW4, 11 interactors
MINTiQ8WTW4
STRINGi9606.ENSP00000232501

Structurei

3D structure databases

ProteinModelPortaliQ8WTW4
SMRiQ8WTW4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 133Interaction with PDPK11 PublicationAdd BLAST133

Sequence similaritiesi

Belongs to the NPR2 family.Curated

Phylogenomic databases

eggNOGiKOG3789 Eukaryota
ENOG410XP7B LUCA
GeneTreeiENSGT00390000001414
HOGENOMiHOG000007022
HOVERGENiHBG055255
InParanoidiQ8WTW4
KOiK20405
OMAiYASMTHG
OrthoDBiEOG091G0759
PhylomeDBiQ8WTW4
TreeFamiTF106159

Family and domain databases

InterProiView protein in InterPro
IPR009348 NPR2
PANTHERiPTHR12991 PTHR12991, 2 hits
PfamiView protein in Pfam
PF06218 NPR2, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8WTW4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGSGCRIECI FFSEFHPTLG PKITYQVPED FISRELFDTV QVYIITKPEL 
        60         70         80         90        100
QNKLITVTAM EKKLIGCPVC IEHKKYSRNA LLFNLGFVCD AQAKTCALEP 
       110        120        130        140        150
IVKKLAGYLT TLELESSFVS MEESKQKLVP IMTILLEELN ASGRCTLPID 
       160        170        180        190        200
ESNTIHLKVI EQRPDPPVAQ EYDVPVFTKD KEDFFNSQWD LTTQQILPYI 
       210        220        230        240        250
DGFRHIQKIS AEADVELNLV RIAIQNLLYY GVVTLVSILQ YSNVYCPTPK 
       260        270        280        290        300
VQDLVDDKSL QEACLSYVTK QGHKRASLRD VFQLYCSLSP GTTVRDLIGR 
       310        320        330        340        350
HPQQLQHVDE RKLIQFGLMK NLIRRLQKYP VRVTREEQSH PARLYTGCHS 
       360        370        380
YDEICCKTGM SYHELDERLE NDPNIIICWK
Length:380
Mass (Da):43,658
Last modified:May 10, 2004 - v2
Checksum:i5ECA201CE073F964
GO
Isoform 2 (identifier: Q8WTW4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-120: Missing.
     312-323: KLIQFGLMKNLI → SEENLLGHLGVT
     324-380: Missing.

Note: No experimental confirmation available.
Show »
Length:203
Mass (Da):23,150
Checksum:i221068DD133A9BA1
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F2Z3D4F2Z3D4_HUMAN
GATOR complex protein NPRL2
NPRL2
57Annotation score:
F2Z2R8F2Z2R8_HUMAN
GATOR complex protein NPRL2
NPRL2
87Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17P → L in AAH21984 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077122105L → P in FFEVF2. 1 PublicationCorresponds to variant dbSNP:rs886037965EnsemblClinVar.1
Natural variantiVAR_077123110T → S in FFEVF2; unknown pathological significance. 1 Publication1
Natural variantiVAR_077124198P → H in FFEVF2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs745518585Ensembl.1
Natural variantiVAR_077125214D → H in FFEVF2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs149128231Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0103291 – 120Missing in isoform 2. 2 PublicationsAdd BLAST120
Alternative sequenceiVSP_010330312 – 323KLIQF…MKNLI → SEENLLGHLGVT in isoform 2. 2 PublicationsAdd BLAST12
Alternative sequenceiVSP_010331324 – 380Missing in isoform 2. 2 PublicationsAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF040707 mRNA Translation: AAC62535.1
AF040708 mRNA Translation: AAC62536.1
AK292196 mRNA Translation: BAF84885.1
CR542035 mRNA Translation: CAG46832.1
AC002481 Genomic DNA Translation: AAB67310.1
CH471055 Genomic DNA Translation: EAW65106.1
CH471055 Genomic DNA Translation: EAW65107.1
BC021984 mRNA Translation: AAH21984.1
BC056861 mRNA Translation: AAH56861.1
CCDSiCCDS2826.1 [Q8WTW4-1]
RefSeqiNP_006536.3, NM_006545.4 [Q8WTW4-1]
UniGeneiHs.437083

Genome annotation databases

EnsembliENST00000232501; ENSP00000232501; ENSG00000114388 [Q8WTW4-1]
GeneIDi10641
KEGGihsa:10641
UCSCiuc003daj.2 human [Q8WTW4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF040707 mRNA Translation: AAC62535.1
AF040708 mRNA Translation: AAC62536.1
AK292196 mRNA Translation: BAF84885.1
CR542035 mRNA Translation: CAG46832.1
AC002481 Genomic DNA Translation: AAB67310.1
CH471055 Genomic DNA Translation: EAW65106.1
CH471055 Genomic DNA Translation: EAW65107.1
BC021984 mRNA Translation: AAH21984.1
BC056861 mRNA Translation: AAH56861.1
CCDSiCCDS2826.1 [Q8WTW4-1]
RefSeqiNP_006536.3, NM_006545.4 [Q8WTW4-1]
UniGeneiHs.437083

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6CESelectron microscopy4.00N1-380[»]
6CETelectron microscopy4.40N1-380[»]
ProteinModelPortaliQ8WTW4
SMRiQ8WTW4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115885, 19 interactors
CORUMiQ8WTW4
DIPiDIP-50746N
IntActiQ8WTW4, 11 interactors
MINTiQ8WTW4
STRINGi9606.ENSP00000232501

PTM databases

iPTMnetiQ8WTW4
PhosphoSitePlusiQ8WTW4

Polymorphism and mutation databases

BioMutaiNPRL2
DMDMi47117604

Proteomic databases

EPDiQ8WTW4
MaxQBiQ8WTW4
PaxDbiQ8WTW4
PeptideAtlasiQ8WTW4
PRIDEiQ8WTW4
ProteomicsDBi74610
74611 [Q8WTW4-2]

Protocols and materials databases

DNASUi10641
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000232501; ENSP00000232501; ENSG00000114388 [Q8WTW4-1]
GeneIDi10641
KEGGihsa:10641
UCSCiuc003daj.2 human [Q8WTW4-1]

Organism-specific databases

CTDi10641
DisGeNETi10641
EuPathDBiHostDB:ENSG00000114388.12
GeneCardsiNPRL2
HGNCiHGNC:24969 NPRL2
HPAiHPA038196
HPA038197
MalaCardsiNPRL2
MIMi607072 gene
617116 phenotype
neXtProtiNX_Q8WTW4
OpenTargetsiENSG00000114388
Orphaneti98820 Familial focal epilepsy with variable foci
PharmGKBiPA165697981
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3789 Eukaryota
ENOG410XP7B LUCA
GeneTreeiENSGT00390000001414
HOGENOMiHOG000007022
HOVERGENiHBG055255
InParanoidiQ8WTW4
KOiK20405
OMAiYASMTHG
OrthoDBiEOG091G0759
PhylomeDBiQ8WTW4
TreeFamiTF106159

Enzyme and pathway databases

SIGNORiQ8WTW4

Miscellaneous databases

ChiTaRSiNPRL2 human
GeneWikiiTUSC4
GenomeRNAii10641
PROiPR:Q8WTW4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114388 Expressed in 112 organ(s), highest expression level in cerebellar hemisphere
CleanExiHS_TUSC4
ExpressionAtlasiQ8WTW4 baseline and differential
GenevisibleiQ8WTW4 HS

Family and domain databases

InterProiView protein in InterPro
IPR009348 NPR2
PANTHERiPTHR12991 PTHR12991, 2 hits
PfamiView protein in Pfam
PF06218 NPR2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiNPRL2_HUMAN
AccessioniPrimary (citable) accession number: Q8WTW4
Secondary accession number(s): A8K831
, Q6FGS2, Q9Y249, Q9Y497
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: November 7, 2018
This is version 133 of the entry and version 2 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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