ID RRAGB_MOUSE Reviewed; 374 AA.
AC Q6NTA4; B1AVD6;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 133.
DE RecName: Full=Ras-related GTP-binding protein B {ECO:0000305};
DE Short=Rag B {ECO:0000250|UniProtKB:Q5VZM2};
DE Short=RagB {ECO:0000250|UniProtKB:Q5VZM2};
DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q5VZM2};
GN Name=Rragb {ECO:0000312|MGI:MGI:3038613};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2] {ECO:0000312|EMBL:AAH69180.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH69180.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH69180.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH SESN1; SESN2 AND SESN3.
RX PubMed=25259925; DOI=10.1016/j.cell.2014.08.038;
RA Peng M., Yin N., Li M.O.;
RT "Sestrins function as guanine nucleotide dissociation inhibitors for Rag
RT GTPases to control mTORC1 signaling.";
RL Cell 159:122-133(2014).
CC -!- FUNCTION: Guanine nucleotide-binding protein that plays a crucial role
CC in the cellular response to amino acid availability through regulation
CC of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with
CC RagC/RRAGC or RagD/RRAGD and cycles between an inactive GDP-bound and
CC an active GTP-bound form: RagB/RRAGB is in its active form when GTP-
CC bound RagB/RRAGB forms a complex with GDP-bound RagC/RRAGC (or
CC RagD/RRAGD) and in an inactive form when GDP-bound RagB/RRAGB
CC heterodimerizes with GTP-bound RagC/RRAGC (or RagD/RRAGD). In its GTP-
CC bound active form, promotes the recruitment of mTORC1 to the lysosomes
CC and its subsequent activation by the GTPase RHEB. Involved in the
CC RCC1/Ran-GTPase pathway. {ECO:0000250|UniProtKB:Q5VZM2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:Q5VZM2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:Q5VZM2};
CC -!- ACTIVITY REGULATION: The activation of GTP-binding proteins is
CC generally mediated by a guanine exchange factor (GEF), while
CC inactivation through hydrolysis of bound GTP is catalyzed by a GTPase
CC activating protein (GAP). The Ragulator complex functions as a GEF and
CC promotes the active GTP-bound form. The GATOR1 complex functions as a
CC GAP and stimulates RRAGB GTPase activity to turn it into its inactive
CC GDP-bound form, preventing mTORC1 recruitment and activation.
CC {ECO:0000250|UniProtKB:Q5VZM2}.
CC -!- SUBUNIT: Interacts with RRAGC and RRAGD; heterodimerization stabilizes
CC RRAG proteins (By similarity). The GTP-bound form of RRAGB (in complex
CC with the GDP-bound form of RRAGC or RRAGD) interacts with RPTOR,
CC thereby promoting recruitment of mTORC1 to the lysosomes (By
CC similarity). Component of the lysosomal folliculin complex (LFC),
CC composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound,
CC RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity).
CC Interacts with SH3BP4; the interaction with this negative regulator is
CC most probably direct, preferentially occurs with the inactive GDP-bound
CC form of RRAGB, is negatively regulated by amino acids and prevents
CC interaction with RPTOR (By similarity). Interacts with the GATOR1
CC complex; inactivates RRAGB (By similarity). The Rag heterodimer
CC interacts with SLC38A9; the probable amino acid sensor. Interacts with
CC SESN1, SESN2 and SESN3 (PubMed:25259925).
CC {ECO:0000250|UniProtKB:Q5VZM2, ECO:0000250|UniProtKB:Q7L523,
CC ECO:0000269|PubMed:25259925}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q5VZM2}.
CC Lysosome membrane {ECO:0000250|UniProtKB:Q5VZM2}. Note=Recruited to the
CC lysosome surface by the Ragulator complex.
CC {ECO:0000250|UniProtKB:Q5VZM2}.
CC -!- SIMILARITY: Belongs to the GTR/RAG GTP-binding protein family.
CC {ECO:0000305}.
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DR EMBL; AL672293; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069180; AAH69180.1; -; mRNA.
DR EMBL; BC070407; AAH70407.1; -; mRNA.
DR CCDS; CCDS30480.1; -.
DR RefSeq; NP_001004154.1; NM_001004154.2.
DR AlphaFoldDB; Q6NTA4; -.
DR SMR; Q6NTA4; -.
DR BioGRID; 232822; 2.
DR STRING; 10090.ENSMUSP00000039013; -.
DR iPTMnet; Q6NTA4; -.
DR PhosphoSitePlus; Q6NTA4; -.
DR SwissPalm; Q6NTA4; -.
DR jPOST; Q6NTA4; -.
DR MaxQB; Q6NTA4; -.
DR PaxDb; 10090-ENSMUSP00000039013; -.
DR PeptideAtlas; Q6NTA4; -.
DR ProteomicsDB; 299814; -.
DR Pumba; Q6NTA4; -.
DR Antibodypedia; 447; 165 antibodies from 26 providers.
DR DNASU; 245670; -.
DR Ensembl; ENSMUST00000039720.11; ENSMUSP00000039013.5; ENSMUSG00000041658.13.
DR GeneID; 245670; -.
DR KEGG; mmu:245670; -.
DR UCSC; uc012hqx.1; mouse.
DR AGR; MGI:3038613; -.
DR CTD; 10325; -.
DR MGI; MGI:3038613; Rragb.
DR VEuPathDB; HostDB:ENSMUSG00000041658; -.
DR eggNOG; KOG3886; Eukaryota.
DR GeneTree; ENSGT00950000183031; -.
DR HOGENOM; CLU_044099_1_1_1; -.
DR InParanoid; Q6NTA4; -.
DR OMA; FEVESRN; -.
DR OrthoDB; 33171at2759; -.
DR PhylomeDB; Q6NTA4; -.
DR TreeFam; TF300616; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-165159; MTOR signalling.
DR Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 245670; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Rragb; mouse.
DR PRO; PR:Q6NTA4; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q6NTA4; Protein.
DR Bgee; ENSMUSG00000041658; Expressed in hypothalamus and 62 other cell types or tissues.
DR ExpressionAtlas; Q6NTA4; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:1990131; C:Gtr1-Gtr2 GTPase complex; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0032561; F:guanyl ribonucleotide binding; ISS:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISO:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:1990253; P:cellular response to leucine starvation; ISO:MGI.
DR GO; GO:0009267; P:cellular response to starvation; IBA:GO_Central.
DR GO; GO:0010507; P:negative regulation of autophagy; IBA:GO_Central.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISO:MGI.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; ISO:MGI.
DR CDD; cd11384; RagA_like; 1.
DR Gene3D; 3.30.450.190; -; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR InterPro; IPR006762; Gtr1_RagA.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039397; RagA/B.
DR PANTHER; PTHR11259; RAS-RELATED GTP BINDING RAG/GTR YEAST; 1.
DR PANTHER; PTHR11259:SF4; RAS-RELATED GTP-BINDING PROTEIN B; 1.
DR Pfam; PF04670; Gtr1_RagA; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; GTP-binding; Hydrolase; Isopeptide bond; Lysosome;
KW Membrane; Nucleotide-binding; Reference proteome; Ubl conjugation.
FT CHAIN 1..374
FT /note="Ras-related GTP-binding protein B"
FT /id="PRO_0000239949"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 49
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 50
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 50
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 51
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 52
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 52
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 53
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 53
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 54
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 54
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 55
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 55
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 69
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 69
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 75
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 75
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 126
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 188
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 188
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 191
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 209
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 225
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 225
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q5VZM2"
FT CROSSLNK 203
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT CROSSLNK 281
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT CROSSLNK 291
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT CROSSLNK 305
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
SQ SEQUENCE 374 AA; 43191 MW; 4F1F13AF06DDA16B CRC64;
MEESDSEKKT EKENVGPKVE PPLGEPEGSL GWAMPNAAMK KKVLLMGKSG SGKTSMRSII
FANYIARDTR RLGATILDRI HSLQINSSLS TYSLVDSVGN TKTFDVEHSH VRFLGNLVLN
LWDCGGQDTF MENYFTSQRD NIFRNVEVLI YVFDVESREL EKDMHYYQSC LEAILQNSPE
AKIFCLVHKM DLVQEDQRDL IFKEREEDLR RLSRPLECSC FRTSIWDETL YKAWSSIVYQ
LIPNVQQLEM NLRNFAEIIE ADEVLLFERA TFLVISHYQC KEQRDAHRFE KISNIIKQFK
LSCSKLAASF QSMEVRNSNF AAFIDIFTSN TYVMVVMSDP SIPSAATLIN IRNARKHFEK
LERVDGPKQC LLMR
//
