ID RRAGD_HUMAN Reviewed; 400 AA.
AC Q9NQL2; A8K184; Q7L8F9; Q9NPG0;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 24-JAN-2024, entry version 157.
DE RecName: Full=Ras-related GTP-binding protein D;
DE Short=Rag D;
DE Short=RagD;
DE EC=3.6.5.- {ECO:0000305|PubMed:24095279};
GN Name=RRAGD {ECO:0000312|HGNC:HGNC:19903};
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:0000305, ECO:0000312|EMBL:AAG32663.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH RRAGA AND RRAGB,
RP 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [3] {ECO:0000305, ECO:0000312|EMBL:AL138717}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4] {ECO:0000312|EMBL:CAB70775.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-49 (ISOFORM 1).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAH03088.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-400 (ISOFORM 1).
RC TISSUE=Lung {ECO:0000312|EMBL:AAH03088.1};
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 [7] {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 [8]
RP INTERACTION WITH RPTOR, AND MUTAGENESIS OF SER-76 AND GLN-121.
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 [9]
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 [10]
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
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 [12]
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 [13]
RP SUBUNIT.
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 [14]
RP SUBUNIT.
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 [15]
RP FUNCTION, AND INTERACTION WITH TFEB.
RX PubMed=32612235; DOI=10.1038/s41586-020-2444-0;
RA Napolitano G., Di Malta C., Esposito A., de Araujo M.E.G., Pece S.,
RA Bertalot G., Matarese M., Benedetti V., Zampelli A., Stasyk T.,
RA Siciliano D., Venuta A., Cesana M., Vilardo C., Nusco E., Monfregola J.,
RA Calcagni A., Di Fiore P.P., Huber L.A., Ballabio A.;
RT "A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dube syndrome.";
RL Nature 585:597-602(2020).
RN [16]
RP INVOLVEMENT IN HOMG7, VARIANTS HOMG7 LEU-76; TRP-76; PRO-97; ARG-119;
RP LEU-119 AND LYS-221, CHARACTERIZATION OF VARIANTS HOMG7 LEU-76; TRP-76;
RP PRO-97; ARG-119; LEU-119 AND LYS-221, AND FUNCTION.
RX PubMed=34607910; DOI=10.1681/asn.2021030333;
RA Schlingmann K.P., Jouret F., Shen K., Nigam A., Arjona F.J., Dafinger C.,
RA Houillier P., Jones D.P., Kleinerueschkamp F., Oh J., Godefroid N.,
RA Eltan M., Gueran T., Burtey S., Parotte M.C., Koenig J., Braun A., Bos C.,
RA Ibars Serra M., Rehmann H., Zwartkruis F.J.T., Renkema K.Y., Klingel K.,
RA Schulze-Bahr E., Schermer B., Bergmann C., Altmueller J., Thiele H.,
RA Beck B.B., Dahan K., Sabatini D., Liebau M.C., Vargas-Poussou R.,
RA Knoers N.V.A.M., Konrad M., de Baaij J.H.F.;
RT "mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy
RT and Cardiomyopathy.";
RL J. Am. Soc. Nephrol. 32:2885-2899(2021).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 60-239 IN COMPLEX WITH GTP ANALOG.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human Ras-related GTP-binding D.";
RL Submitted (FEB-2009) to the PDB data bank.
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:24095279,
CC PubMed:34607910). Forms heterodimeric Rag complexes with RagA/RRAGA or
CC RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-
CC bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD
CC forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an
CC inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound
CC RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279). In its active form,
CC promotes the recruitment of mTORC1 to the lysosomes and its subsequent
CC activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This
CC is a crucial step in the activation of the MTOR signaling cascade by
CC amino acids (PubMed:20381137, PubMed:24095279). Also plays a central
CC role in the non-canonical mTORC1 complex, which acts independently of
CC RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB
CC and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors
CC TFEB and TFE3 (PubMed:32612235). {ECO:0000269|PubMed:20381137,
CC ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:32612235,
CC ECO:0000269|PubMed:34607910}.
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:0000305|PubMed:24095279};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000305|PubMed:24095279};
CC -!- ACTIVITY REGULATION: The activation of RagD/RRAGD is mediated by a
CC GTPase activating protein (GAP) (PubMed:24095279). In high-amino acid
CC conditions, activated by GTPase activating protein FLCN that stimulates
CC RRAGD GTPase activity to turn it into its active GDP-bound form
CC (PubMed:24095279). In response to amino acid depletion, the GATOR1
CC complex inactivates RagC/RRAGC by securing the GTP-bound inactive form
CC (By similarity). {ECO:0000250|UniProtKB:Q9HB90,
CC ECO:0000269|PubMed:24095279}.
CC -!- SUBUNIT: Forms a heterodimer with RRAGA in a sequence-independent
CC manner and RRAGB (PubMed:11073942, PubMed:14660641). Heterodimerization
CC stabilizes RRAG proteins (PubMed:11073942, PubMed:14660641,
CC PubMed:25561175, PubMed:25567906). The GDP-bound form of RRAGD (in
CC complex with the GTP-bound form of RRAGA or RRAGB), interacts with
CC RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes
CC (PubMed:18497260). 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 NOL8 (PubMed:14660641). Interacts with SH3BP4; the
CC interaction with this negative regulator is most probably direct,
CC preferentially occurs with the inactive GDP-bound form of RRAGD and is
CC negatively regulated by amino acids (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). The GDP-bound form interacts with TFEB (By
CC similarity). The GDP-bound form interacts with TFE3 (PubMed:32612235).
CC {ECO:0000250|UniProtKB:Q7TT45, ECO:0000250|UniProtKB:Q9HB90,
CC ECO:0000269|PubMed:11073942, ECO:0000269|PubMed:14660641,
CC ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:22575674,
CC ECO:0000269|PubMed:25259925, ECO:0000269|PubMed:25561175,
CC ECO:0000269|PubMed:25567906, ECO:0000269|PubMed:32612235}.
CC -!- INTERACTION:
CC Q9NQL2; Q9P2J5: LARS1; NbExp=13; IntAct=EBI-992949, EBI-356077;
CC Q9NQL2; Q7L523: RRAGA; NbExp=9; IntAct=EBI-992949, EBI-752376;
CC Q9NQL2; Q5VZM2: RRAGB; NbExp=7; IntAct=EBI-992949, EBI-993049;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11073942}. Nucleus
CC {ECO:0000269|PubMed:11073942}. Lysosome membrane
CC {ECO:0000269|PubMed:20381137}. Note=Predominantly cytoplasmic
CC (PubMed:11073942). Recruited to the lysosome surface by the Ragulator
CC complex (PubMed:20381137). 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 ECO:0000269|PubMed:20381137}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:11073942};
CC IsoId=Q9NQL2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:14574404};
CC IsoId=Q9NQL2-2; Sequence=VSP_052078;
CC -!- DISEASE: Hypomagnesemia 7, renal, with or without dilated
CC cardiomyopathy (HOMG7) [MIM:620152]: An autosomal dominant renal
CC disease characterized by hypomagnesemia, hypokalemia, salt wasting, and
CC nephrocalcinosis. A subset of patients develop severe dilated
CC cardiomyopathy. {ECO:0000269|PubMed:34607910}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the GTR/RAG GTP-binding protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH03088.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF272036; AAG32663.1; -; mRNA.
DR EMBL; AK289799; BAF82488.1; -; mRNA.
DR EMBL; AL138717; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48554.1; -; Genomic_DNA.
DR EMBL; AL137502; CAB70775.2; -; mRNA.
DR EMBL; BC003088; AAH03088.1; ALT_INIT; mRNA.
DR CCDS; CCDS5022.1; -. [Q9NQL2-1]
DR PIR; T46254; T46254.
DR RefSeq; NP_067067.1; NM_021244.4. [Q9NQL2-1]
DR PDB; 2Q3F; X-ray; 2.10 A; A/B=60-239.
DR PDBsum; 2Q3F; -.
DR AlphaFoldDB; Q9NQL2; -.
DR SMR; Q9NQL2; -.
DR BioGRID; 121848; 36.
DR ComplexPortal; CPX-2513; RAG guanosine triphosphatase complex, RAGA-RAGD variant.
DR ComplexPortal; CPX-767; RAG guanosine triphosphatase complex, RAGB-RAGD variant.
DR IntAct; Q9NQL2; 11.
DR STRING; 9606.ENSP00000358423; -.
DR GlyGen; Q9NQL2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQL2; -.
DR PhosphoSitePlus; Q9NQL2; -.
DR SwissPalm; Q9NQL2; -.
DR BioMuta; RRAGD; -.
DR DMDM; 74752904; -.
DR EPD; Q9NQL2; -.
DR jPOST; Q9NQL2; -.
DR MassIVE; Q9NQL2; -.
DR MaxQB; Q9NQL2; -.
DR PaxDb; 9606-ENSP00000358423; -.
DR PeptideAtlas; Q9NQL2; -.
DR ProteomicsDB; 82161; -. [Q9NQL2-1]
DR ProteomicsDB; 82162; -. [Q9NQL2-2]
DR Pumba; Q9NQL2; -.
DR Antibodypedia; 31866; 151 antibodies from 27 providers.
DR DNASU; 58528; -.
DR Ensembl; ENST00000359203.3; ENSP00000352131.2; ENSG00000025039.15. [Q9NQL2-2]
DR Ensembl; ENST00000369415.9; ENSP00000358423.4; ENSG00000025039.15. [Q9NQL2-1]
DR GeneID; 58528; -.
DR KEGG; hsa:58528; -.
DR MANE-Select; ENST00000369415.9; ENSP00000358423.4; NM_021244.5; NP_067067.1.
DR UCSC; uc003pnd.5; human. [Q9NQL2-1]
DR AGR; HGNC:19903; -.
DR CTD; 58528; -.
DR DisGeNET; 58528; -.
DR GeneCards; RRAGD; -.
DR HGNC; HGNC:19903; RRAGD.
DR HPA; ENSG00000025039; Tissue enhanced (skeletal).
DR MalaCards; RRAGD; -.
DR MIM; 608268; gene.
DR MIM; 620152; phenotype.
DR neXtProt; NX_Q9NQL2; -.
DR OpenTargets; ENSG00000025039; -.
DR PharmGKB; PA134957148; -.
DR VEuPathDB; HostDB:ENSG00000025039; -.
DR eggNOG; KOG3887; Eukaryota.
DR GeneTree; ENSGT00950000183031; -.
DR HOGENOM; CLU_047421_1_1_1; -.
DR InParanoid; Q9NQL2; -.
DR OMA; NCRTFQE; -.
DR OrthoDB; 166730at2759; -.
DR PhylomeDB; Q9NQL2; -.
DR TreeFam; TF300659; -.
DR PathwayCommons; Q9NQL2; -.
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; Q9NQL2; -.
DR SIGNOR; Q9NQL2; -.
DR BioGRID-ORCS; 58528; 23 hits in 1149 CRISPR screens.
DR ChiTaRS; RRAGD; human.
DR EvolutionaryTrace; Q9NQL2; -.
DR GenomeRNAi; 58528; -.
DR Pharos; Q9NQL2; Tbio.
DR PRO; PR:Q9NQL2; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9NQL2; Protein.
DR Bgee; ENSG00000025039; Expressed in body of tongue and 220 other cell types or tissues.
DR Genevisible; Q9NQL2; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
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:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IMP:CAFA.
DR GO; GO:0003924; F:GTPase activity; IMP:CAFA.
DR GO; GO:0051020; F:GTPase binding; IPI:CAFA.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0071233; P:cellular response to leucine; IMP:CAFA.
DR GO; GO:1990253; P:cellular response to leucine starvation; IMP:CAFA.
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; NAS:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR CDD; cd11385; RagC_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; IPR039400; RagC/D.
DR PANTHER; PTHR11259; RAS-RELATED GTP BINDING RAG/GTR YEAST; 1.
DR PANTHER; PTHR11259:SF5; RAS-RELATED GTP-BINDING PROTEIN D; 1.
DR Pfam; PF04670; Gtr1_RagA; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cardiomyopathy; Cytoplasm;
KW Disease variant; GTP-binding; Hydrolase; Lysosome; Membrane;
KW Nucleotide-binding; Nucleus; Primary hypomagnesemia; Reference proteome.
FT CHAIN 1..400
FT /note="Ras-related GTP-binding protein D"
FT /id="PRO_0000239953"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 12..29
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 71
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 72
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 72
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 73
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 73
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 74
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 74
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 75
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 75
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 76
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 76
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 77
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 77
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 91
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 91
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 95
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 97
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 97
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 120
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 179
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 179
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 180
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 180
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 182
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 182
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT BINDING 220
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 221
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:Q9HB90"
FT BINDING 221
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|Ref.17, ECO:0007744|PDB:2Q3F"
FT VAR_SEQ 1..151
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14574404"
FT /id="VSP_052078"
FT VARIANT 76
FT /note="S -> L (in HOMG7; increased positive regulation of
FT TORC1 signaling; increased phosphorylation of the
FT downstream molecule S6K1)"
FT /evidence="ECO:0000269|PubMed:34607910"
FT /id="VAR_087904"
FT VARIANT 76
FT /note="S -> W (in HOMG7; increased positive regulation of
FT TORC1 signaling; increased phosphorylation of the
FT downstream molecule S6K1)"
FT /evidence="ECO:0000269|PubMed:34607910"
FT /id="VAR_087905"
FT VARIANT 97
FT /note="T -> P (in HOMG7; increased positive regulation of
FT TORC1 signaling; increased phosphorylation of the
FT downstream molecule S6K1)"
FT /evidence="ECO:0000269|PubMed:34607910"
FT /id="VAR_087906"
FT VARIANT 119
FT /note="P -> L (in HOMG7; increased positive regulation of
FT TORC1 signaling; increased phosphorylation of the
FT downstream molecule S6K1)"
FT /evidence="ECO:0000269|PubMed:34607910"
FT /id="VAR_087907"
FT VARIANT 119
FT /note="P -> R (in HOMG7; increased positive regulation of
FT TORC1 signaling; increased phosphorylation of the
FT downstream molecule S6K1)"
FT /evidence="ECO:0000269|PubMed:34607910"
FT /id="VAR_087908"
FT VARIANT 221
FT /note="I -> K (in HOMG7; increased positive regulation of
FT TORC1 signaling; increased phosphorylation of the
FT downstream molecule S6K1)"
FT /evidence="ECO:0000269|PubMed:34607910"
FT /id="VAR_087909"
FT MUTAGEN 76
FT /note="S->L: Increased RPTOR-binding."
FT /evidence="ECO:0000269|PubMed:18497260"
FT MUTAGEN 121
FT /note="Q->L: Decreased RPTOR-binding."
FT /evidence="ECO:0000269|PubMed:18497260"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:2Q3F"
FT HELIX 75..84
FT /evidence="ECO:0007829|PDB:2Q3F"
FT HELIX 88..93
FT /evidence="ECO:0007829|PDB:2Q3F"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:2Q3F"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:2Q3F"
FT HELIX 131..136
FT /evidence="ECO:0007829|PDB:2Q3F"
FT STRAND 138..146
FT /evidence="ECO:0007829|PDB:2Q3F"
FT HELIX 152..168
FT /evidence="ECO:0007829|PDB:2Q3F"
FT STRAND 173..179
FT /evidence="ECO:0007829|PDB:2Q3F"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:2Q3F"
FT HELIX 188..206
FT /evidence="ECO:0007829|PDB:2Q3F"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:2Q3F"
FT HELIX 225..235
FT /evidence="ECO:0007829|PDB:2Q3F"
SQ SEQUENCE 400 AA; 45588 MW; 96FF0854B11AA1BC CRC64;
MSQVLGKPQP QDEDDAEEEE EEDELVGLAD YGDGPDSSDA DPDSGTEEGV LDFSDPFSTE
VKPRILLMGL RRSGKSSIQK VVFHKMSPNE TLFLESTNKI CREDVSNSSF VNFQIWDFPG
QIDFFDPTFD YEMIFRGTGA LIFVIDSQDD YMEALARLHL TVTRAYKVNT DINFEVFIHK
VDGLSDDHKI ETQRDIHQRA NDDLADAGLE KIHLSFYLTS IYDHSIFEAF SKVVQKLIPQ
LPTLENLLNI FISNSGIEKA FLFDVVSKIY IATDSTPVDM QTYELCCDMI DVVIDISCIY
GLKEDGAGTP YDKESTAIIK LNNTTVLYLK EVTKFLALVC FVREESFERK GLIDYNFHCF
RKAIHEVFEV RMKVVKSRKV QNRLQKKKRA TPNGTPRVLL
//
