Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q12980 (NPRL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nitrogen permease regulator 3-like protein
Alternative name(s):
-14 gene protein
Alpha-globin regulatory element-containing gene protein
Protein CGTHBA
Gene names
Name:NPRL3
Synonyms:C16orf35, CGTHBA, MARE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length569 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

As a component of the GATOR1 complex, 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. Ref.6

Subunit structure

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. Ref.6

Tissue specificity

Widely expressed.

Involvement in disease

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 (Ref.6).

Sequence similarities

Belongs to the NPR3 family.

Caution

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

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NPRL2Q8WTW41EBI-2650314,EBI-1043552

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 569569Nitrogen permease regulator 3-like protein
PRO_0000220638

Experimental info

Sequence conflict4891Missing in CAI94885. Ref.2
Sequence conflict4891Missing in CAI95611. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q12980 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 44BEF42AA7F2841D

FASTA56963,605
        10         20         30         40         50         60 
MRDNTSPISV ILVSSGSRGN KLLFRYPFQR SQEHPASQTS KPRSRYAASN TGDHADEQDG 

        70         80         90        100        110        120 
DSRFSDVILA TILATKSEMC GQKFELKIDN VRFVGHPTLL QHALGQISKT DPSPKREAPT 

       130        140        150        160        170        180 
MILFNVVFAL RANADPSVIN CLHNLSRRIA TVLQHEERRC QYLTREAKLI LALQDEVSAM 

       190        200        210        220        230        240 
ADGNEGPQSP FHHILPKCKL ARDLKEAYDS LCTSGVVRLH INSWLEVSFC LPHKIHYAAS 

       250        260        270        280        290        300 
SLIPPEAIER SLKAIRPYHA LLLLSDEKSL LGELPIDCSP ALVRVIKTTS AVKNLQQLAQ 

       310        320        330        340        350        360 
DADLALLQVF QLAAHLVYWG KAIIIYPLCE NNVYMLSPNA SVCLYSPLAE QFSHQFPSHD 

       370        380        390        400        410        420 
LPSVLAKFSL PVSLSEFRNP LAPAVQETQL IQMVVWMLQR RLLIQLHTYV CLMASPSEEE 

       430        440        450        460        470        480 
PRPREDDVPF TARVGGRSLS TPNALSFGSP TSSDDMTLTS PSMDNSSAEL LPSGDSPLNQ 

       490        500        510        520        530        540 
RMTENLLASL SEHERAAILS VPAAQNPEDL RMFARLLHYF RGRHHLEEIM YNENTRRSQL 

       550        560 
LMLFDKFRSV LVVTTHEDPV IAVFQALLP 

« Hide

References

« Hide 'large scale' references
[1]"Conservation of position and sequence of a novel, widely expressed gene containing the major human alpha-globin regulatory element."
Vyas P., Vickers M.A., Picketts D.J., Higgs D.
Genomics 29:679-689(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter."
De Gobbi M., Viprakasit V., Hughes J.R., Fisher C., Buckle V.J., Ayyub H., Gibbons R.J., Vernimmen D., Yoshinaga Y., de Jong P., Cheng J.-F., Rubin E.M., Wood W.G., Bowden D., Higgs D.R.
Science 312:1215-1217(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex."
Neklesa T.K., Davis R.W.
PLoS Genet. 5:E1000515-E1000515(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NPRL2.
[6]"A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1."
Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A., Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M.
Science 340:1100-1106(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN GATOR COMPLEX, INTERACTION WITH RRAG PROTEINS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001070818.1. NM_001077350.2.
UniGeneHs.19699.

3D structure databases

ProteinModelPortalQ12980.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113796. 7 interactions.
IntActQ12980. 1 interaction.

PTM databases

PhosphoSiteQ12980.

Polymorphism databases

DMDM18202492.

Proteomic databases

MaxQBQ12980.
PaxDbQ12980.
PRIDEQ12980.

Protocols and materials databases

DNASU8131.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000399953; ENSP00000382834; ENSG00000103148.
GeneID8131.
KEGGhsa:8131.
UCSCuc002cfq.3. human.

Organism-specific databases

CTD8131.
GeneCardsGC16M000134.
HGNCHGNC:14124. NPRL3.
HPAHPA011741.
MIM600928. gene.
neXtProtNX_Q12980.
PharmGKBPA25550.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324281.
HOGENOMHOG000004787.
HOVERGENHBG019399.
InParanoidQ12980.
OrthoDBEOG7M0NR3.
PhylomeDBQ12980.
TreeFamTF105965.

Gene expression databases

ArrayExpressQ12980.
BgeeQ12980.
CleanExHS_C16orf35.
GenevestigatorQ12980.

Family and domain databases

InterProIPR005365. NPR3.
[Graphical view]
PANTHERPTHR13153. PTHR13153. 1 hit.
PfamPF03666. NPR3. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNPRL3. human.
GenomeRNAi8131.
NextBio30797.
PROQ12980.
SOURCESearch...

Entry information

Entry nameNPRL3_HUMAN
AccessionPrimary (citable) accession number: Q12980
Secondary accession number(s): D3DU40 expand/collapse secondary AC list , Q1W6H0, Q4TT56, Q92469
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: November 1, 1996
Last modified: May 14, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM