RRAGD_MOUSE
ID RRAGD_MOUSE Reviewed; 449 AA.
AC Q7TT45; Q6GTT2; Q9CYC2;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Ras-related GTP-binding protein D;
DE Short=Rag D;
DE Short=RagD;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q9NQL2};
GN Name=Rragd {ECO:0000312|MGI:MGI:1098604};
GN Synonyms=Ragd {ECO:0000312|EMBL:AAP40334.1};
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:AAP40334.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-258.
RA Shan Z., Popescu N.C.;
RT "Isolation and characterization of a mouse GTP-binding protein.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAH38137.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 67-449.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH38137.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH38137.1};
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] {ECO:0000305, ECO:0000312|EMBL:BAB30954.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 111-449.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB30954.2};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAB30954.2};
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 [4]
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 [5]
RP INTERACTION WITH TFE3.
RX PubMed=30595499; DOI=10.1016/j.stem.2018.11.021;
RA Villegas F., Lehalle D., Mayer D., Rittirsch M., Stadler M.B., Zinner M.,
RA Olivieri D., Vabres P., Duplomb-Jego L., De Bont E.S.J.M., Duffourd Y.,
RA Duijkers F., Avila M., Genevieve D., Houcinat N., Jouan T., Kuentz P.,
RA Lichtenbelt K.D., Thauvin-Robinet C., St-Onge J., Thevenon J.,
RA van Gassen K.L.I., van Haelst M., van Koningsbruggen S., Hess D.,
RA Smallwood S.A., Riviere J.B., Faivre L., Betschinger J.;
RT "Lysosomal signaling licenses embryonic stem cell differentiation via
RT inactivation of Tfe3.";
RL Cell Stem Cell 24:257-270(2019).
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 RRAGA or RRAGB and cycles between an inactive GTP-bound and an active
CC GDP-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. This is a crucial step in the activation of the TOR signaling
CC cascade by amino acids. {ECO:0000250|UniProtKB:Q9NQL2}.
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:Q9NQL2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:Q9NQL2};
CC -!- ACTIVITY REGULATION: In high-amino acid conditions, activated by GTPase
CC activating protein (GAP) FLCN that stimulates RRAGD GTPase activity to
CC turn it into its active GDP-bound form. {ECO:0000250|UniProtKB:Q9NQL2}.
CC -!- SUBUNIT: Forms a heterodimer with RRAGA in a sequence-independent
CC manner and RRAGB. Heterodimerization stabilizes RRAG proteins. In
CC complex with RRAGB, interacts with RPTOR; this interaction is
CC particularly efficient with GTP-loaded RRAGB and GDP-loaded RRAGC (By
CC similarity). Component of the lysosomal folliculin complex (LFC),
CC composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound,
CC RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (By similarity).
CC Interacts with NOL8. Interacts with SH3BP4; the interaction with this
CC negative regulator is most probably direct, preferentially occurs with
CC the inactive GDP-bound form of RRAGD and is negatively regulated by
CC amino acids (By similarity). The Rag heterodimer interacts with
CC SLC38A9; the probable amino acid sensor. Interacts with SESN1, SESN2
CC and SESN3 (PubMed:25259925). The GDP-bound form interacts with TFE3
CC (PubMed:30595499). {ECO:0000250|UniProtKB:Q9HB90,
CC ECO:0000250|UniProtKB:Q9NQL2, ECO:0000269|PubMed:25259925,
CC ECO:0000269|PubMed:30595499}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NQL2}. Nucleus
CC {ECO:0000250|UniProtKB:Q9NQL2}. Lysosome
CC {ECO:0000250|UniProtKB:Q9NQL2}. Note=Predominantly cytoplasmic. May
CC shuttle between the cytoplasm and nucleus, depending on the bound
CC nucleotide state of associated RRAGA. {ECO:0000250|UniProtKB:Q9NQL2}.
CC -!- SIMILARITY: Belongs to the GTR/RAG GTP-binding protein family.
CC {ECO:0000305}.
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DR EMBL; AF490406; AAP40334.1; -; mRNA.
DR EMBL; BC038137; AAH38137.1; -; mRNA.
DR EMBL; AK017818; BAB30954.2; -; mRNA.
DR RefSeq; NP_081767.2; NM_027491.2.
DR AlphaFoldDB; Q7TT45; -.
DR SMR; Q7TT45; -.
DR BioGRID; 206438; 1.
DR iPTMnet; Q7TT45; -.
DR PhosphoSitePlus; Q7TT45; -.
DR SwissPalm; Q7TT45; -.
DR jPOST; Q7TT45; -.
DR MaxQB; Q7TT45; -.
DR PRIDE; Q7TT45; -.
DR ProteomicsDB; 262706; -.
DR DNASU; 52187; -.
DR GeneID; 52187; -.
DR KEGG; mmu:52187; -.
DR UCSC; uc008sfm.1; mouse.
DR CTD; 58528; -.
DR MGI; MGI:1098604; Rragd.
DR InParanoid; Q7TT45; -.
DR OrthoDB; 1216811at2759; -.
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; 52187; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Rragd; mouse.
DR PRO; PR:Q7TT45; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q7TT45; protein.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:1990131; C:Gtr1-Gtr2 GTPase complex; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
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:0019003; F:GDP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IBA:GO_Central.
DR GO; GO:0071233; P:cellular response to leucine; ISO:MGI.
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:0032008; P:positive regulation of TOR signaling; IBA:GO_Central.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR CDD; cd11385; RagC_like; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR006762; Gtr1_RagA.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039400; RagC/D.
DR PANTHER; PTHR11259; PTHR11259; 1.
DR Pfam; PF04670; Gtr1_RagA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; GTP-binding; Hydrolase; Lysosome; Nucleotide-binding; Nucleus;
KW Reference proteome.
FT CHAIN 1..449
FT /note="Ras-related GTP-binding protein D"
FT /id="PRO_0000239954"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 118..126
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NQL2"
FT BINDING 166..170
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q00582"
FT BINDING 228..231
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q00582"
FT CONFLICT 111
FT /note="K -> M (in Ref. 3; BAB30954)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="L -> S (in Ref. 3; BAB30954)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="F -> L (in Ref. 3; BAB30954)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="F -> C (in Ref. 2; AAH38137)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="K -> M (in Ref. 3; BAB30954)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 449 AA; 51232 MW; 6D9AC2A86DE5784A CRC64;
MSQVLGKPQP QGEDGGEDQE EDELVGLAGY EDGPESSDAE LDSGPEEGES RRNSWMPRSW
CSEATRHECW EPGLWRSSHL LGIGGGWRML RRQRQADFFL DFSDPFSTEV KPRILLMGLR
RSGKSSIQKV VFHKMSPSET LFLESTNRIC REDVSNSSFV NFQIWDFPGQ IDFFDPTFDY
EMIFRGTGAL IFVIDSQDDY MEALARLHLT VTRAYKVNTD INFEVFIHKV DGLSDDHKIE
TQRDIHQRAN DDLADAGLEK IHLSFYLTSI YDHSIFEAFS KVVQKLIPQL PTLENLLNIF
ISNSGIEKAF LFDVVSKIYI ATDSTPVDMQ TYELCCDMID VVIDISCIYG LKEDGAGAPY
DKDSTAIIKL NNTTVLYLKE VTKFLALVCF VREESFERKG LIDYNFHCFR KAIHEVFEVR
MKMVKSRKAQ SRLPKKTGAT PNGTPRVLL
