RRAGC_HUMAN
ID RRAGC_HUMAN Reviewed; 399 AA.
AC Q9HB90; Q9H202; Q9H8Q8;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Ras-related GTP-binding protein C;
DE Short=Rag C;
DE Short=RagC;
DE EC=3.6.5.- {ECO:0000269|PubMed:11073942, ECO:0000305|PubMed:24095279};
DE AltName: Full=GTPase-interacting protein 2;
DE AltName: Full=TIB929;
GN Name=RRAGC {ECO:0000312|HGNC:HGNC:19902};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000312|EMBL:AAG45221.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11145883; DOI=10.1006/viro.2000.0738;
RA Horwitz M.S.;
RT "Adenovirus immunoregulatory genes and their cellular targets.";
RL Virology 279:1-8(2001).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAG32662.1}
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, INTERACTION WITH RRAGA AND
RP RRAGB, SUBCELLULAR LOCATION, AND GTP-BINDING.
RX PubMed=11073942; DOI=10.1074/jbc.m004389200;
RA Sekiguchi T., Hirose E., Nakashima N., Ii M., Nishimoto T.;
RT "Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag
RT A and Rag B.";
RL J. Biol. Chem. 276:7246-7257(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4] {ECO:0000312|EMBL:AAH16668.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph {ECO:0000312|EMBL:AAH16668.1};
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 [5] {ECO:0000305, ECO:0000312|EMBL:BAB14548.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 266-399.
RC TISSUE=Ovary {ECO:0000312|EMBL:BAB14548.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6] {ECO:0000305}
RP INTERACTION WITH NOL8 AND RRAGA.
RX PubMed=14660641; DOI=10.1074/jbc.m305935200;
RA Sekiguchi T., Todaka Y., Wang Y., Hirose E., Nakashima N., Nishimoto T.;
RT "A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG
RT A/C/D.";
RL J. Biol. Chem. 279:8343-8350(2004).
RN [7]
RP INTERACTION WITH RPTOR, AND MUTAGENESIS OF SER-75 AND GLN-120.
RX PubMed=18497260; DOI=10.1126/science.1157535;
RA Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C.,
RA Bar-Peled L., Sabatini D.M.;
RT "The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1.";
RL Science 320:1496-1501(2008).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20381137; DOI=10.1016/j.cell.2010.02.024;
RA Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M.;
RT "Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is
RT necessary for its activation by amino acids.";
RL Cell 141:290-303(2010).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INTERACTION WITH SH3BP4.
RX PubMed=22575674; DOI=10.1016/j.molcel.2012.04.007;
RA Kim Y.M., Stone M., Hwang T.H., Kim Y.G., Dunlevy J.R., Griffin T.J.,
RA Kim D.H.;
RT "SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1
RT signaling.";
RL Mol. Cell 46:833-846(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-15, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP SER-75 AND GLN-120.
RX PubMed=24095279; DOI=10.1016/j.molcel.2013.09.016;
RA Tsun Z.Y., Bar-Peled L., Chantranupong L., Zoncu R., Wang T., Kim C.,
RA Spooner E., Sabatini D.M.;
RT "The folliculin tumor suppressor is a GAP for the RagC/D GTPases that
RT signal amino acid levels to mTORC1.";
RL Mol. Cell 52:495-505(2013).
RN [14]
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP INTERACTION WITH SLC38A9.
RX PubMed=25561175; DOI=10.1038/nature14107;
RA Rebsamen M., Pochini L., Stasyk T., de Araujo M.E., Galluccio M.,
RA Kandasamy R.K., Snijder B., Fauster A., Rudashevskaya E.L., Bruckner M.,
RA Scorzoni S., Filipek P.A., Huber K.V., Bigenzahn J.W., Heinz L.X.,
RA Kraft C., Bennett K.L., Indiveri C., Huber L.A., Superti-Furga G.;
RT "SLC38A9 is a component of the lysosomal amino acid sensing machinery that
RT controls mTORC1.";
RL Nature 519:477-481(2015).
RN [17]
RP INTERACTION WITH SLC38A9.
RX PubMed=25567906; DOI=10.1126/science.1257132;
RA Wang S., Tsun Z.Y., Wolfson R.L., Shen K., Wyant G.A., Plovanich M.E.,
RA Yuan E.D., Jones T.D., Chantranupong L., Comb W., Wang T., Bar-Peled L.,
RA Zoncu R., Straub C., Kim C., Park J., Sabatini B.L., Sabatini D.M.;
RT "Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine
RT sufficiency to mTORC1.";
RL Science 347:188-194(2015).
RN [18] {ECO:0007744|PDB:6ULG}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.31 ANGSTROMS) IN COMPLEX WITH FLCN;
RP FNIP2; RRAGA; LAMTOR1; LAMTOR2; LAMTOR3; LAMTOR4 AND LAMTOR5, AND
RP IDENTIFICATION IN THE LFC COMPLEX.
RX PubMed=31704029; DOI=10.1016/j.cell.2019.10.036;
RA Shen K., Rogala K.B., Chou H.T., Huang R.K., Yu Z., Sabatini D.M.;
RT "Cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex.";
RL Cell 179:1319-1329(2019).
RN [19] {ECO:0007744|PDB:6NZD}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) IN COMPLEX WITH FLCN;
RP FNIP2; RRAGA; LAMTOR1; LAMTOR2; LAMTOR3; LAMTOR4 AND LAMTOR5, AND
RP IDENTIFICATION IN THE LFC COMPLEX.
RX PubMed=31672913; DOI=10.1126/science.aax0364;
RA Lawrence R.E., Fromm S.A., Fu Y., Yokom A.L., Kim D.J., Thelen A.M.,
RA Young L.N., Lim C.Y., Samelson A.J., Hurley J.H., Zoncu R.;
RT "Structural mechanism of a Rag GTPase activation checkpoint by the
RT lysosomal folliculin complex.";
RL Science 366:971-977(2019).
RN [20]
RP VARIANT TYR-75, CHARACTERIZATION OF VARIANT TYR-75, INVOLVEMENT IN DISEASE,
RP AND FUNCTION.
RX PubMed=27234373; DOI=10.1007/s00439-016-1685-3;
RA Long P.A., Zimmermann M.T., Kim M., Evans J.M., Xu X., Olson T.M.;
RT "De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal
RT dilated cardiomyopathy.";
RL Hum. Genet. 135:909-917(2016).
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 (PubMed:20381137, PubMed:27234373,
CC PubMed:24095279). Forms heterodimeric Rag complexes with RRAGA or RRAGB
CC and cycles between an inactive GTP-bound and an active GDP-bound form
CC (PubMed:24095279). In its active form participates in the
CC relocalization of mTORC1 to the lysosomes and its subsequent activation
CC by the GTPase RHEB (PubMed:20381137, PubMed:27234373, PubMed:24095279).
CC This is a crucial step in the activation of the TOR signaling cascade
CC by amino acids (PubMed:20381137, PubMed:27234373, PubMed:24095279).
CC {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279,
CC ECO:0000269|PubMed:27234373}.
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:0000269|PubMed:11073942, ECO:0000305|PubMed:24095279};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000269|PubMed:11073942, ECO:0000305|PubMed:24095279};
CC -!- ACTIVITY REGULATION: In high-amino acid conditions, activated by GTPase
CC activating protein (GAP) FLCN that stimulates RRAGC GTPase activity to
CC turn it into its active GDP-bound form. {ECO:0000269|PubMed:24095279}.
CC -!- SUBUNIT: Forms a heterodimer with RRAGA, in a sequence-independent
CC manner, and RRAGB (PubMed:11073942, PubMed:14660641).
CC Heterodimerization stabilizes proteins of the heterodimer
CC (PubMed:11073942). In complex with RRAGA or RRAGB, interacts with
CC RPTOR; this interaction is particularly efficient with GTP-loaded RRAGB
CC and GDP-loaded RRAGC (PubMed:18497260). Component of the lysosomal
CC folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2),
CC RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound,
CC and Ragulator (PubMed:31704029, PubMed:31672913). Interacts with NOL8
CC (PubMed:14660641). Interacts with SH3BP4; the interaction with this
CC negative regulator is most probably direct, preferentially occurs with
CC the inactive GDP-bound form of RRAGB, is negatively regulated by amino
CC acids and prevents interaction with RPTOR (PubMed:22575674). The Rag
CC heterodimer interacts with SLC38A9; the probable amino acid sensor
CC (PubMed:25561175, PubMed:25567906). Interacts with SESN1, SESN2 and
CC SESN3 (PubMed:25259925). Interacts with PIP4P1 (By similarity). The
CC GDP-bound form interacts with TFE3 (By similarity).
CC {ECO:0000250|UniProtKB:Q99K70, ECO:0000269|PubMed:11073942,
CC ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:18497260,
CC ECO:0000269|PubMed:22575674, ECO:0000269|PubMed:25259925,
CC ECO:0000269|PubMed:25561175, ECO:0000269|PubMed:25567906,
CC ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:31704029}.
CC -!- INTERACTION:
CC Q9HB90; Q7L523: RRAGA; NbExp=20; IntAct=EBI-752390, EBI-752376;
CC Q9HB90; Q5VZM2: RRAGB; NbExp=8; IntAct=EBI-752390, EBI-993049;
CC Q9HB90; Q8NBW4: SLC38A9; NbExp=12; IntAct=EBI-752390, EBI-9978316;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11073942}. Nucleus
CC {ECO:0000269|PubMed:11073942}. Lysosome {ECO:0000269|PubMed:20381137}.
CC Note=Predominantly cytoplasmic. May shuttle between the cytoplasm and
CC nucleus, depending on the bound nucleotide state of associated RRAGA
CC (PubMed:11073942). {ECO:0000269|PubMed:11073942}.
CC -!- DISEASE: Note=RRAGC mutations have been found in a patient with
CC idiopathic dilated cardiomyopathy with ventricular dilation and
CC systolic dysfunction, bilateral cataracts, and mild facial
CC dysmorphisms. {ECO:0000269|PubMed:27234373}.
CC -!- SIMILARITY: Belongs to the GTR/RAG GTP-binding protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14548.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF323609; AAG45221.1; -; mRNA.
DR EMBL; AF272035; AAG32662.1; -; mRNA.
DR EMBL; AL139260; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016668; AAH16668.1; -; mRNA.
DR EMBL; AK023373; BAB14548.1; ALT_INIT; mRNA.
DR CCDS; CCDS430.1; -.
DR RefSeq; NP_001258780.1; NM_001271851.1.
DR RefSeq; NP_071440.1; NM_022157.3.
DR PDB; 3LLU; X-ray; 1.40 A; A=60-237.
DR PDB; 6CES; EM; 4.00 A; C=1-399.
DR PDB; 6EHR; X-ray; 2.90 A; G=239-399.
DR PDB; 6NZD; EM; 3.60 A; G=1-399.
DR PDB; 6S6A; X-ray; 2.63 A; C/D=1-399.
DR PDB; 6S6D; X-ray; 2.50 A; C/D=1-399.
DR PDB; 6SB0; EM; 5.50 A; D/J=1-399.
DR PDB; 6SB2; EM; 6.20 A; D/J=1-399.
DR PDB; 6U62; EM; 3.18 A; C=2-399.
DR PDB; 6ULG; EM; 3.31 A; G=1-399.
DR PDB; 6WJ2; EM; 3.20 A; G=1-399.
DR PDB; 6WJ3; EM; 3.90 A; G=1-399.
DR PDB; 7T3A; EM; 4.00 A; L=1-399.
DR PDB; 7T3B; EM; 3.90 A; E=1-399.
DR PDB; 7T3C; EM; 4.00 A; E/L=1-399.
DR PDBsum; 3LLU; -.
DR PDBsum; 6CES; -.
DR PDBsum; 6EHR; -.
DR PDBsum; 6NZD; -.
DR PDBsum; 6S6A; -.
DR PDBsum; 6S6D; -.
DR PDBsum; 6SB0; -.
DR PDBsum; 6SB2; -.
DR PDBsum; 6U62; -.
DR PDBsum; 6ULG; -.
DR PDBsum; 6WJ2; -.
DR PDBsum; 6WJ3; -.
DR PDBsum; 7T3A; -.
DR PDBsum; 7T3B; -.
DR PDBsum; 7T3C; -.
DR AlphaFoldDB; Q9HB90; -.
DR SMR; Q9HB90; -.
DR BioGRID; 122074; 50.
DR DIP; DIP-37515N; -.
DR IntAct; Q9HB90; 26.
DR MINT; Q9HB90; -.
DR STRING; 9606.ENSP00000362092; -.
DR GlyGen; Q9HB90; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9HB90; -.
DR MetOSite; Q9HB90; -.
DR PhosphoSitePlus; Q9HB90; -.
DR BioMuta; RRAGC; -.
DR DMDM; 74752776; -.
DR EPD; Q9HB90; -.
DR jPOST; Q9HB90; -.
DR MassIVE; Q9HB90; -.
DR MaxQB; Q9HB90; -.
DR PaxDb; Q9HB90; -.
DR PeptideAtlas; Q9HB90; -.
DR PRIDE; Q9HB90; -.
DR ProteomicsDB; 81509; -.
DR Antibodypedia; 17665; 289 antibodies from 28 providers.
DR DNASU; 64121; -.
DR Ensembl; ENST00000373001.4; ENSP00000362092.3; ENSG00000116954.8.
DR GeneID; 64121; -.
DR KEGG; hsa:64121; -.
DR MANE-Select; ENST00000373001.4; ENSP00000362092.3; NM_022157.4; NP_071440.1.
DR UCSC; uc001ccq.4; human.
DR CTD; 64121; -.
DR DisGeNET; 64121; -.
DR GeneCards; RRAGC; -.
DR HGNC; HGNC:19902; RRAGC.
DR HPA; ENSG00000116954; Low tissue specificity.
DR MIM; 608267; gene.
DR neXtProt; NX_Q9HB90; -.
DR OpenTargets; ENSG00000116954; -.
DR PharmGKB; PA134862062; -.
DR VEuPathDB; HostDB:ENSG00000116954; -.
DR eggNOG; KOG3887; Eukaryota.
DR GeneTree; ENSGT00950000183031; -.
DR HOGENOM; CLU_047421_1_1_1; -.
DR InParanoid; Q9HB90; -.
DR OMA; RACSHQA; -.
DR OrthoDB; 1216811at2759; -.
DR PhylomeDB; Q9HB90; -.
DR TreeFam; TF300659; -.
DR PathwayCommons; Q9HB90; -.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-165159; MTOR signalling.
DR Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; Q9HB90; -.
DR SIGNOR; Q9HB90; -.
DR BioGRID-ORCS; 64121; 169 hits in 1091 CRISPR screens.
DR ChiTaRS; RRAGC; human.
DR EvolutionaryTrace; Q9HB90; -.
DR GeneWiki; RRAGC; -.
DR GenomeRNAi; 64121; -.
DR Pharos; Q9HB90; Tbio.
DR PRO; PR:Q9HB90; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9HB90; protein.
DR Bgee; ENSG00000116954; Expressed in islet of Langerhans and 112 other tissues.
DR Genevisible; Q9HB90; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1990131; C:Gtr1-Gtr2 GTPase complex; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:HGNC-UCL.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0051020; F:GTPase binding; IPI:CAFA.
DR GO; GO:0000287; F:magnesium ion binding; NAS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IGI: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:0032008; P:positive regulation of TOR signaling; IBA:GO_Central.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR GO; GO:0032006; P:regulation of TOR signaling; IGI:UniProtKB.
DR GO; GO:1903432; P:regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; IMP:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; NAS:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; NAS:UniProtKB.
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 3D-structure; Acetylation; Cytoplasm; Disease variant; GTP-binding;
KW Hydrolase; Lysosome; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231"
FT CHAIN 2..399
FT /note="Ras-related GTP-binding protein C"
FT /id="PRO_0000239951"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 68..75
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P53290"
FT BINDING 116..120
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q00582"
FT BINDING 178..181
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P53290"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 96
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99K70"
FT VARIANT 75
FT /note="S -> Y (found in a patient with idiopathic dilated
FT cardiomyopathy; renders cells partially insensitive to
FT amino acid deprivation and result in activated mTORC1
FT signaling)"
FT /evidence="ECO:0000269|PubMed:27234373"
FT /id="VAR_076511"
FT MUTAGEN 75
FT /note="S->L: Increased RPTOR-binding."
FT /evidence="ECO:0000269|PubMed:18497260"
FT MUTAGEN 75
FT /note="S->N: Reduced affinity for all nucleotides, but with
FT preferential binding of GDP over GTP, leading to activate
FT mTORC1."
FT /evidence="ECO:0000269|PubMed:24095279"
FT MUTAGEN 120
FT /note="Q->L: Maintains GTP-bound state, leading to
FT inactivate mTORC1. Decreased RPTOR-binding."
FT /evidence="ECO:0000269|PubMed:18497260,
FT ECO:0000269|PubMed:24095279"
FT CONFLICT 206
FT /note="A -> S (in Ref. 1; AAG45221)"
FT /evidence="ECO:0000305"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:3LLU"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:6U62"
FT HELIX 74..82
FT /evidence="ECO:0007829|PDB:3LLU"
FT HELIX 87..92
FT /evidence="ECO:0007829|PDB:3LLU"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:3LLU"
FT TURN 105..108
FT /evidence="ECO:0007829|PDB:6ULG"
FT STRAND 112..116
FT /evidence="ECO:0007829|PDB:3LLU"
FT HELIX 130..135
FT /evidence="ECO:0007829|PDB:3LLU"
FT STRAND 138..145
FT /evidence="ECO:0007829|PDB:3LLU"
FT HELIX 151..167
FT /evidence="ECO:0007829|PDB:3LLU"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:3LLU"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:3LLU"
FT HELIX 185..205
FT /evidence="ECO:0007829|PDB:3LLU"
FT STRAND 213..218
FT /evidence="ECO:0007829|PDB:3LLU"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:6WJ2"
FT HELIX 224..235
FT /evidence="ECO:0007829|PDB:3LLU"
FT HELIX 240..252
FT /evidence="ECO:0007829|PDB:6S6D"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:6S6D"
FT STRAND 257..263
FT /evidence="ECO:0007829|PDB:6S6D"
FT TURN 264..267
FT /evidence="ECO:0007829|PDB:6S6D"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:6S6D"
FT HELIX 279..298
FT /evidence="ECO:0007829|PDB:6S6D"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:6S6A"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:6S6D"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:6S6D"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:6S6D"
FT STRAND 324..330
FT /evidence="ECO:0007829|PDB:6S6D"
FT STRAND 332..342
FT /evidence="ECO:0007829|PDB:6S6D"
FT HELIX 343..346
FT /evidence="ECO:0007829|PDB:6S6D"
FT HELIX 349..366
FT /evidence="ECO:0007829|PDB:6S6D"
FT TURN 367..370
FT /evidence="ECO:0007829|PDB:6U62"
SQ SEQUENCE 399 AA; 44224 MW; 35B3171253CC69CF CRC64;
MSLQYGAEET PLAGSYGAAD SFPKDFGYGV EEEEEEAAAA GGGVGAGAGG GCGPGGADSS
KPRILLMGLR RSGKSSIQKV VFHKMSPNET LFLESTNKIY KDDISNSSFV NFQIWDFPGQ
MDFFDPTFDY EMIFRGTGAL IYVIDAQDDY MEALTRLHIT VSKAYKVNPD MNFEVFIHKV
DGLSDDHKIE TQRDIHQRAN DDLADAGLEK LHLSFYLTSI YDHSIFEAFS KVVQKLIPQL
PTLENLLNIF ISNSGIEKAF LFDVVSKIYI ATDSSPVDMQ SYELCCDMID VVIDVSCIYG
LKEDGSGSAY DKESMAIIKL NNTTVLYLKE VTKFLALVCI LREESFERKG LIDYNFHCFR
KAIHEVFEVG VTSHRSCGHQ TSASSLKALT HNGTPRNAI
