RRAGA_MOUSE
ID RRAGA_MOUSE Reviewed; 313 AA.
AC Q80X95; B1AXR0; Q8C1S2; Q8CFU3;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Ras-related GTP-binding protein A {ECO:0000305};
DE Short=Rag A {ECO:0000250|UniProtKB:Q7L523};
DE Short=RagA {ECO:0000250|UniProtKB:Q7L523};
DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q7L523};
GN Name=Rraga {ECO:0000312|MGI:MGI:1915691};
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] {ECO:0000312|EMBL:BAE25953.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC25103.1};
RC TISSUE=Liver {ECO:0000312|EMBL:BAC25103.1}, and
RC Lung {ECO:0000312|EMBL:BAE25953.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
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 [3] {ECO:0000312|EMBL:AAH48245.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH48245.1};
RC TISSUE=Eye {ECO:0000312|EMBL:AAH37615.1}, and
RC Olfactory epithelium {ECO:0000312|EMBL:AAH48245.1};
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
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).
RN [6]
RP INTERACTION WITH PIP4P1.
RX PubMed=29644770; DOI=10.1111/gtc.12583;
RA Hashimoto Y., Shirane M., Nakayama K.I.;
RT "TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1
RT activation.";
RL Genes Cells 23:418-434(2018).
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 RRAGC or RRAGD and cycles between an inactive GDP-bound and an active
CC GTP-bound form. In its active form participates in the relocalization
CC of mTORC1 to the lysosomes and its subsequent activation by the GTPase
CC RHEB. Involved in the RCC1/Ran-GTPase pathway. May play a direct role
CC in a TNF-alpha signaling pathway leading to induction of cell death.
CC {ECO:0000250|UniProtKB:Q7L523}.
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:Q7L523};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:Q7L523};
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 GATOR1 complex functions as a GAP and
CC stimulates RRAGA GTPase activity to turn it into its inactive GDP-bound
CC form. {ECO:0000250|UniProtKB:Q7L523}.
CC -!- SUBUNIT: Can occur as a homodimer or as a heterodimer with RRAGC or
CC RRAGD in a sequence-independent manner; heterodimerization stabilizes
CC proteins of the heterodimer. In complex with RRAGC, but not with RRAGB,
CC interacts with RPTOR. The GTP-bound form of RRAGA interacts with NOL8.
CC Component of the lysosomal folliculin complex (LFC), composed of FLCN,
CC FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or
CC RRAGD/RagD GTP-bound, and Ragulator. Interacts with SH3BP4; the
CC interaction with this negative regulator is most probably direct,
CC preferentially occurs with the inactive GDP-bound form of RRAGA and is
CC negatively regulated by amino acids. The Rag heterodimer interacts with
CC SLC38A9; the probable amino acid sensor. Interacts (inactive GDP-bound
CC form) with RNF152; stimulated by amino acid starvation. Interacts
CC (polyubiquitinated) with the GATOR1 complex; inactivates RRAGA.
CC Interacts (polyubiquitinated) with TSC2 (By similarity). Interacts with
CC SESN1, SESN2 and SESN3 (PubMed:25259925). Interacts with PIP4P1
CC (PubMed:29644770). Interacts with GPR137B (By similarity).
CC {ECO:0000250|UniProtKB:P42345, ECO:0000250|UniProtKB:Q7L523,
CC ECO:0000269|PubMed:25259925, ECO:0000269|PubMed:29644770}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q7L523}. Nucleus
CC {ECO:0000250|UniProtKB:Q7L523}. Lysosome
CC {ECO:0000250|UniProtKB:Q7L523}.
CC -!- PTM: Ubiquitinated. 'Lys-68'-linked polyubiquitination of the GDP-bound
CC inactive form of RRAGA at Lys-142, Lys-220, Lys-230 and Lys-244 by
CC RNF152 is increased in response to amino acid starvation.
CC Polyubiquitination promotes interaction with the GATOR1 complex. This
CC does not affect RRAGA degradation. {ECO:0000250|UniProtKB:Q7L523}.
CC -!- SIMILARITY: Belongs to the GTR/RAG GTP-binding protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH37615.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC25103.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK004955; BAC25103.1; ALT_FRAME; mRNA.
DR EMBL; AK144591; BAE25953.1; -; mRNA.
DR EMBL; AL824707; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037615; AAH37615.1; ALT_INIT; mRNA.
DR EMBL; BC048245; AAH48245.1; -; mRNA.
DR CCDS; CCDS18306.1; -.
DR RefSeq; NP_848463.1; NM_178376.3.
DR AlphaFoldDB; Q80X95; -.
DR SMR; Q80X95; -.
DR BioGRID; 212856; 12.
DR IntAct; Q80X95; 4.
DR STRING; 10090.ENSMUSP00000088591; -.
DR iPTMnet; Q80X95; -.
DR PhosphoSitePlus; Q80X95; -.
DR SwissPalm; Q80X95; -.
DR EPD; Q80X95; -.
DR jPOST; Q80X95; -.
DR MaxQB; Q80X95; -.
DR PaxDb; Q80X95; -.
DR PeptideAtlas; Q80X95; -.
DR PRIDE; Q80X95; -.
DR ProteomicsDB; 299881; -.
DR Antibodypedia; 42790; 183 antibodies from 25 providers.
DR DNASU; 68441; -.
DR Ensembl; ENSMUST00000091064; ENSMUSP00000088591; ENSMUSG00000070934.
DR GeneID; 68441; -.
DR KEGG; mmu:68441; -.
DR UCSC; uc008tlw.2; mouse.
DR CTD; 10670; -.
DR MGI; MGI:1915691; Rraga.
DR VEuPathDB; HostDB:ENSMUSG00000070934; -.
DR eggNOG; KOG3886; Eukaryota.
DR GeneTree; ENSGT00950000183031; -.
DR HOGENOM; CLU_044099_1_0_1; -.
DR InParanoid; Q80X95; -.
DR OMA; QQKDHIF; -.
DR OrthoDB; 951213at2759; -.
DR PhylomeDB; Q80X95; -.
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-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 68441; 19 hits in 75 CRISPR screens.
DR ChiTaRS; Rraga; mouse.
DR PRO; PR:Q80X95; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q80X95; protein.
DR Bgee; ENSMUSG00000070934; Expressed in animal zygote and 248 other tissues.
DR Genevisible; Q80X95; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:1990130; C:GATOR1 complex; ISO:MGI.
DR GO; GO:1990131; C:Gtr1-Gtr2 GTPase complex; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IBA:GO_Central.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045918; P:negative regulation of cytolysis; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IBA:GO_Central.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR GO; GO:0042268; P:regulation of cytolysis; ISO:MGI.
DR GO; GO:1903432; P:regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; ISS:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR CDD; cd11384; RagA_like; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR006762; Gtr1_RagA.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039397; RagA/B.
DR PANTHER; PTHR11259; PTHR11259; 2.
DR Pfam; PF04670; Gtr1_RagA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; GTP-binding; Hydrolase; Isopeptide bond; Lysosome;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..313
FT /note="Ras-related GTP-binding protein A"
FT /id="PRO_0000239946"
FT BINDING 14..21
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 62..66
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q00582"
FT BINDING 127..130
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT BINDING 164
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT CROSSLNK 142
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT CROSSLNK 220
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT CROSSLNK 230
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
FT CROSSLNK 244
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q7L523"
SQ SEQUENCE 313 AA; 36566 MW; B0DA1FC8FA6B766A CRC64;
MPNTAMKKKV LLMGKSGSGK TSMRSIIFAN YIARDTRRLG ATIDVEHSHV RFLGNLVLNL
WDCGGQDTFM ENYFTSQRDN IFRNVEVLIY VFDVESRELE KDMHYYQSCL EAILQNSPDA
KIFCLVHKMD LVQEDQRDLI FKEREEDLRR LSRPLECACF RTSIWDETLY KAWSSIVYQL
IPNVQQLEMN LRNFAQIIEA DEVLLFERAT FLVISHYQCK EQRDVHRFEK ISNIIKQFKL
SCSKLAASFQ SMEVRNSNFA AFIDIFTSNT YVMVVMSDPS IPSAATLINI RNARKHFEKL
ERVDGPKHSL LMR
